Methods using human calcium sensor protein, fragments thereof and DNA encoding same

ABSTRACT

The present invention relates to the isolation of a cDNA clone encoding the calcium sensor in human placenta and subsequent Northern blots confirming the mRNA expression also in human parathyroid and kidney tubule cells. Close sequence similarity is demonstrated with the rat  Heymann nephritis  antigen, a glycoprotein of the kidney tubule brush border with calcium binding ability. Immunohistochemistry substantiates a tissue distribution of the calcium sensor protein similar to that previously described for the Heymann antigen. It is proposed that the identified calcium sensor protein constitutes a universal sensor for recognition of variation in extracellular calcium, and that it plays a key role for calcium regulation via different organ systems. The calcium sensor protein belongs to the LDL-superfamily of glycoproteins, claimed to function primarily as protein receptors, but with functionally important calcium binding capacity.

This application is a continuation-in-part of PCT/US95/15203 filed onNov. 22, 1995, which is a continuation-in-part of Ser. No. 08/487,314filed Jun. 7,1995, which is a continuation-in-part of Ser. No.08/344,836 filed Nov. 23, 1994, now abandoned, which is acontinuation-in-part of PCT/SE94/00483 filed May 24,1994.

BACKGROUND OF THE INVENTION

The present invention relates to a cDNA clone encoding a human calciumsensor protein of parathyroid, placental, and kidney tubule cells.

In WO 88/03271 there is described monoclonal antiparathyroid antibodiesidentifying a parathyroid cell membrane-bound calcium receptor orsensor, crucially involved in calcium regulation of the parathyroidhormone (PTH) release (1,2). The receptor function is essential formaintenance of normal plasma calcium concentrations, and reducedreceptor expression within proliferating parathyroid cells of patientswith hyperparathyroidism (HPT) results in calcium insensitivity of thePTH secretion and variably severe hypercalcemia (3-6). Reactivity withthe antiparathyroid antibodies was also demonstrated for proximal kidneytubule cells and cytotrophoblast cells of the human placenta, and thecytotrophoblasts were demonstrated to exhibit an almostparathyroid-identical regulation of cytoplasmic calcium [Ca²⁺i] (7,8).The antibody-reactive structure was found to exert calcium sensingfunction also in the cytotrophoblasts, and as these cells constitutepart of the syncytium, the calcium sensor was suggested to be activelyinvolved in the calcium homeostasis of the fetus (7,8). It was proposedthat the antibody-reactive structure of the proximal kidney tubule cellsexerts a similar calcium sensing function, and that the calcium sensor,thus, plays a more universal role in calcium regulation via differentorgan systems (1,7,9,10).

On HPT patients with hypercalcemia, surgery is performed to remove oneor more of the parathyroid glands. It would be greatly desirable to havealternatives to this surgical procedure as HPT has proven to be a verycommon disorder and surgery is a relatively costly procedure andsometimes even entails some risks for the patients.

The calcium sensor/receptor has been revealed as a 500 kDa single chainglycoprotein (7). However, the amino acid sequence as well as thecorresponding DNA sequences thereof are hitherto unknown.

SUMMARY OF THE INVENTION

Therefore, an object of the present invention was to provide sufficientstructural data of the calcium sensor/receptor to enable completecharacterization thereof.

In one embodiment, the present invention provides complete amino acidsequence of the human calcium sensor protein of parathyroid, placentaland kidney tubule cells.

In another embodiment the invention provides nucleic acid sequenceencoding the human calcium sensor and nucleic acid probes foridentifying other novel calcium sensor proteins.

Another object is to use said structural data to design novel treatmentmethods as well as compounds and compositions for treating calciumrelated disorders.

In other embodiments, the present invention provides identification ofpeptide regions within the calcium sensor protein cytoplasmic domainwhich are homologous to SH2 and SH3 binding motifs involved in signaltransduction pathways.

Two important human diseases associated with perturbations of thecalcium ion homeostasis are hyperthyroidism and osteoporosis. Thus, inone embodiment cells expressing the calcium sensor protein or a fragmentthereof or comprising the cDNA encoding the calcium sensor protein ofthe present invention may be utilized in an assay to identify moleculeswhich block or enhance the activity of the calcium sensor protein,including signal transduction pathways associated with the activity ofthe sensor. These molecules will be useful in the treatment of mammalianpathological conditions associated with perturbations in the levels ofPTH, vitamins D3 production, estrogen, osteoclast activity or osteoblastactivity (therefore, bone resorption and/or formation), calciumsecretion and calcium ion homeostasis.

The present invention describes the isolation and characterization ofcDNA clones encoding the calcium sensor/receptor in human placenta andNorthern blots verifying the presence of the corresponding mRNA withinthe parathyroid and kidney. Close sequence similarity between thecalcium sensor and a rat Heymann nephritis antigen, gp330 (11, 67),suggests that the common calcium sensor of the placenta, the parathyroidand kidney tubule is related to this antigen, represents the humanhomologue of gp330, and belongs to a family of large glycoproteins withreceptor function and calcium binding ability. Therefore, a furtherobject of this invention is to provide diagnostic assays and therapeuticmethods based on human gp330.

The invention provides a method of identifying agonists and/orantagonists of human calcium sensor protein activity comprisingcontacting potential agonists or antagonists with said calcium sensorprotein or a biologically active sequence analog thereof and determiningthe ability of said potential agonists or antagonists to block orenhance the activity of said calcium sensor protein or biologicallyactive sequence analog thereof.

The present invention further provides a method of identifying agonistsand/or antagonists of human calcium sensor protein activity comprising:

a) expressing a cDNA encoding a human calcium sensor protein or abiologically active sequence analog thereof in a host cell;

b) contacting potential agonists or antagonists with said host cell; and

c) determining the ability of said agonists or antagonists to block orenhance the activity of said calcium sensor protein or fragment thereof.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1. Isolation by HPLC of peptides obtained after digestion of thecalcium sensor protein with Lys-C endoprotease (solid line). Dashed linerepresents the chromatography of an identical reaction where thecalcium-sensor was omitted. The flow rate was kept at 100 μl/min. Twopeptide fractions which gave easily interpretable sequences are denotedby arrows.

FIG. 2. Sequences of two Lys-C peptides (SEQ ID Nos. 1 and 2) isolatedby HPLC of the calcium-sensor protein.

FIG. 3. Partial nucleotide sequence (SEQ ID No. 3) and deduced aminoacid sequence (SEQ ID No. 4) of the-cDNA clone, pCAS-2, encoding part ofthe calcium-sensor protein. Portions of the deduced amino acid sequenceidentical to the peptides 292 and 293 are underlined.

FIG. 4. Alignment of the amino acid sequence of the calcium-sensorprotein (SEQ ID No. 4) to corresponding portions of the Heymann antigen(HEYMANN, SEQ ID No. 5), low density lipoprotein receptor (LDL-RC, SEQID No. 6), and LDL related receptor protein (LDLRRP, SEQ ID No. 7).Stars denote residues identical between the calcium sensor protein andany of the other sequences. X denotes a position in the Heymann antigensequence where identity has not been published.

FIG. 5. Northern blot analysis of total RNA from parathyroid adenoma(1), kidney (2), liver (3), placenta (4), pancreas (5), adrenal gland(6), small gut (7). Filters were hybridized with the 2.8 kb pCAS-2insert probe, and reactions visualized by a phosphorimager. Locations of28S and 18S ribosomal RNA are indicated.

FIGS. 6A-6E. Complete nucleotide (SEQ ID No. 11) and amino acid (SEQ IDNo. 12) sequence of the human calcium sensor 2.8 kb cDNA clone. Thetransmembrane domain of the sensor is shown in bold type. The three SH3binding regions are underlined or overlined and the SH2 binding regionis shown in strikethru.

FIG. 7. Amino acid sequence of the calcium sensor cytoplasmic domain(SEQ ID No. 13) and comparison of the three calcium sensor SH3 bindingregions (SEQ ID Nos. 14-16) to known SH3 binding motifs (SEQ ID Nos.20-37).

FIG. 8. Comparison of relative binding strengths between a calciumsensor SH3 binding region and various GST fusion proteins comprising anSH3 domain.

FIG. 9. Comparison of the calcium sensor SH2 binding region (SEQ ID No.19) with amino acid sequence requirements necessary for interaction withthe SH2 region of the p85 regulatory subunit of PI3K (SEQ ID Nos.38-78).

FIG. 10. Structure of human gp330, including the EGF repeat, growthfactor repeats and YWTD spacer regions. N depicts the amino terminus ofthe protein and C the carboxyl-terminus. The arrow indicates thelocation of the transmembrane region.

FIG. 11. Strategy for extending CAS sequence from pCAS-2.

FIG. 12. Comparison of the same region within different CAS cDNAsequences revealing amino acid sequence differences.

DETAILED DESCRIPTION OF PREFERRED EMBODIMENTS

Unless indicated otherwise herein, the following terms have theindicated meanings.

The term “polypeptide” means a linear array of amino acids connected oneto the other by peptide bonds between the α-amino and carboxy groups ofadjacent amino acids.

“Substantially purified” is used herein to mean “substantiallyhomogeneous”, which is defined as a material which is substantially freeof compounds normally associated with it in its natural state (e.g.,other proteins or peptides, carbohydrates, lipids). “Substantiallypurified” is not meant to exclude artificial or synthetic mixtures withother compounds. The term is also not meant to exclude the presence ofimpurities which do not interfere with biological activity, and whichmay be present, for example, due to incomplete purification orcompounding with a pharmaceutically acceptable preparation.

The term “biologically active polypeptide” means the naturally occurringpolypeptide per se as well as biologically active analogues thereof,including synthetically produced polypeptides and analogues thereof, aswell as natural and pharmaceutically acceptable salts andpharmaceutically acceptable derivatives thereof. The term “biologicallyactive polypeptide” also encompasses biologically active fragmentsthereof, as well as “biologically active sequence analogues” thereof.Different forms of the peptide may exist. These variations may becharacterized by difference in the nucleotide sequence of the structuralgene coding for proteins of identical biological function.

The term “biologically active sequence analogue” includes nonnaturallyoccurring analogues having single or multiple amino acid substitutions,deletions, additions, or replacements. All such allelic variations,modifications, and analogues resulting in derivatives which retain oneor more of the native biologically active properties are included withinthe scope of this invention.

In this application, nucleotides are indicated by their bases using thefollowing standard one-letter abbreviations:

Guanine G Adenine A Thymine T Cytosine C Unknown N

In this application, amino acid residues are indicated using thefollowing standard one-letter abbreviations:

Alanine A Cysteine C Aspartic Acid D Glutamic Acid E Phenylalanine FGlycine G Histidine H Isoleucine I Lysine K Leucine L Methionine MAsparagine N Proline P Glutamine Q Arginine R Serine S Threonine TValine V Tryptophan W Tyrosine Y Unknown X

The term “amino acid” as used herein is meant to denote the aboverecited natural amino acids and functional equivalents thereof.

This invention provides isolated nucleic acid molecules encoding acommon calcium sensor protein of parathyroid, placental and kidneytubule cells and comprising a coding sequence selected from the groupconsisting of SEQ ID No. 3, SEQ ID No. 11, SEQ ID No. 83, SEQ ID No. 85,SEQ ID No. 87, and SEQ ID No. 89.

Furthermore, this invention provides a vector comprising an isolatednucleic acid molecule encoding the calcium sensor protein or a fragmentthereof which encodes functional regions of the sensor.

Moreover, the invention provides a method of preparing calcium sensorprotein which comprises inserting a nuleic acid encoding the calciumsensor or a fragment thereof in a suitable vector, inserting theresulting vector in a suitable host cell, recovering the calcium sensorprotein produced by the resulting cell, and purifying the calcium sensorprotein so recovered. This method for preparing a calcium sensor proteinor fragment thereof uses recombinant DNA technology methods which arewell known in the art. Alternatively, the calcium sensor protein or afragment thereof may be prepared using standard solid phase methodologyof peptide synthesis.

The present invention also provides antisense nucleic acids which can beused to down regulate or block the expression of the calcium sensorprotein either in vitro, ex vivo or in vivo. The down regulation of geneexpression can be made at both translational or transcriptional levels.Antisense nucleic acids of the invention are more preferentially RNAfragments capable of specifically hybridizing with all or part of thesequence selected from the group consisting of SEQ ID No. 3, SEQ ID No.11, SEQ ID No. 83, SEQ ID No. 85, SEQ ID No. 87, and SEQ ID No. 89 orthe corresponding messenger RNA. These antisense can be syntheticoligonucleotides prepared based on the sequence selected from the groupconsisting of SEQ ID No. 3, SEQ ID No. 11, SEQ ID No. 83, SEQ ID No. 85,SEQ ID No. 87, and SEQ ID No. 89, optionally modified to improve theirstability of selectivity, as disclosed for instance in EP 92574. Theycan also be DNA sequences whose expression in the cell produces RNAcomplementary to all or part of the calcium sensor protein mRNA. Theseantisenses can be prepared by expression of all or part of the sequenceselected from the group consisting of SEQ ID No. 3, SEQ ID No. 11, SEQID No. 83, SEQ ID No. 85, SEQ ID No. 87, and SEQ ID No. 89 in theopposite orientation (EP 140 308).

Material and Methods

Tissue specimens. Samples of human parathyroid glands were obtained atsurgery of patients with primary HPT. Other human tissue specimens(kidney, epididymis, liver, pancreas, adrenal gland, small gut, spleen,lung and striated muscle) were sampled from organs removed at surgery.Human placental tissue was collected in conjunction with uncomplicatedpregnancies at full term. All specimens were immediately quick-frozen inisopentane and stored at −70° C.

Isolation of the calcium sensor protein from human placenta. The 500 kDacalcium sensor protein was isolated and purified, from altogether 25human placentas, by immunosorbent and ion exchange chromatographies,following a previously described protocol (7). The procedure utilizestwo different monoclonal antiparathyroid antibodies (1,7), E11 and G11,known to bind different epitopes of the calcium sensing protein; E11 hasdisplayed no functional effect, while G11 efficiently blocks calciumregulation in both parathyroid and placental cells (1,7). Afterpurification, the calcium sensor protein preparation was subjected togel chromatography on a Zorbax GF25 gel column (9.2×250 mm), prior toenzymatic digestion.

The biologically active calcium sensor protein of the present inventionhas been isolated as described. It can also be prepared by chemicalsynthesis in a recombinant DNA biosystem. Biologically active fragmentsof the calcium sensor protein can also be prepared using synthetic orrecombinant technologies which are known in the art.

Cleavage and sequence determination of isolated peptides. Cleavage ofthe 500 kDa protein with endoprotease Lys C from Achromobacter lyticusgenerated peptides, which were subjected to separation on a Brownleemicrobore C₄ column (2.2×30 30 mm), equilibrated in 5% acetonitrile in0.02% trifluoroacetic acid. A linear gradient of 5 to 60% acetonitrilein 0.02% trifluoroacetic acid was employed for peptide elution,monitored at 214 nm using Waters 990 diod-array detector (MilliporeCorporation, Millford, Mass.). Amino terminal sequences of the 35peptides were determined in an ABI 470A gas-phase sequenator, equippedwith an ABI 120A PTH-amino acid chromatograph (Applied Biosystems,Foster City, Calif., USA).

Oligonucleotide synthesis. Oligonucleotides were synthesized 40 using anABI 381 oligonucleotide synthesizer (Applied Biosystems). The followingoligonucleotide mixture was utilized as a probe for screening of theplacental cDNA library:

CCA ATA IAG CTG ATC CTC AAA GAT ATC IAG IGA ATA IGG ATT CAT IGC (SEQ IDNo. 8)     G           G       G       G           G       G Thefollowing two oligonucleotides were synthesized for use in PCRreactions: GCG GAATTC GTA ATG CAA CCA GAC GG (SEQ ID No. 9)             C       G   C   T              G           G             T           T ATA GGATCC  TG ATC CTC AAA AAT ATC (SEQ IDNo. 10)                G   T   G   G   G                            T

The first nine nucleotides contain an EcoR I and a BamH I site,respectively, and the remaining nucleotides correspond to amino acidresidues 1 to 6 of peptides 293 and to residues 8 to 13 of peptide 292.

Screening of a placental cDNA library with a mixed 30 oligonucleotideprobe. A placental 1 gt 11 cDNA library (Clontech, Calif., USA) wasplated out to a density of approximately 2×10⁵ plaques within a 20×25 cmagar plate. Replicate filters (Hybond-N+, Amersham) of ten plates wereprehybridized in 5×SSPE (SSPE; 120 mM NaCl, 8 mM NaH₂PO₄, 0.8 mM EDTA,pH 7.4), 5×Denhart's solution (12), 0.5% SDS, 20 μg/ml single strandedsalmon sperm DNA (Sigma Chemical Co., S:t Louis, Ohio). The mixedoligonucleotide probe, endlabeled with γ-[³²p]-ATP and polynucleotidekinase (Amersham), was added to the hybridization mixture (30×10⁶ cpm in50 ml), and hybridization was carried out over night at 42° C. Thefilter was washed twice in 2×SSPE and once in 0.1×SSPE, exposed to anautoradiography screen and analysed by a phosphorimager (MolecularDynamics, Image Count S.W, Sun Valley Calif.).

PCR reaction. Part of the λ gt 11 cDNA clone CAS-1 was amplified by PCRusing two degenerated probes corresponding to portions of peptides 292and 293. The following conditions were used: 170 ng template DNA, 1 pmolof each oligonucleotide mixture as primers, dNTP 3 mM, Taq-polymerase0.75 u. The reaction was carried out in 20 μl of 10 mM Tris-HCl, pH 8.0,1.5 mM MgCl₂, 50 mM KCl in a Perkin-Elmer 9600 PCR-machine(Perkin-Elmer, Norwalk, USA). Two cycles of denaturation at 94° C. for 2min. annealing at 47° C. for 1 min and extension at 72° C. for 1 min 30sec were followed by 33 cycles of 94° C. for 1 min. 54° C. for 45 sec.72° C. for 1 min and a final extension at 72° C. for 10 min.

Screening of a placental cDNA library with a PCR-fragment as probe. Aplacental λ ZAP-II cDNA library, was screened with the PCR-fragment fromthe cDNA clone CAS-1 labeled by random priming as the probe. Thescreening was carried out as above. 2×10⁶ plaques distributed on ten20×25 cm agar plates were screened.

Nucleotide sequence determination. The insert of the phage clone CAS-2was released from the phage vector in the Bluescript+ vector using ahelper phage (Stratagene, La Jolla, Calif.). Nucleotide sequencereactions were carried out according to the cycle sequencing procedure,utilizing a kit from Applied Biosystems. Sequences were analyzed in anABI 373 A DNA sequenator using the Data Collection Program VIII software(Applied Biosystems). Completion of the CAS-2 2.8 kb cDNA sequence wasaccomplished by the dideoxynucleotide chain-termination method withSequenase (United States Biochemical) and is shown in FIG. 6 (SEQ ID No.11). Multiple sequencing analyses were performed on both strands ofCAS-2 to confirm the sequence. Amino acid sequence deduced from the cDNAsequence was analyzed by a Macvector DNA/RNA software analysis package(Macintosh).

Reverse transcriptase PCR amplification and standard 32p-labeled probescreening of human lambda kidney cDNA libraries were used to completethe cloning of the CAS cDNA (SEQ ID No. 83).

Full-length human placental (SEQ ID No. 85), kidney (SEQ ID No. 87) andparathyroid (SEQ ID No. 89) CAS cDNA sequences were obtained from PCRamplified human placental, kidney and parathyroid cDNA libraries asfollows. Specifically primed first-strand cDNA was prepared usingoligonucleotide primers designed off SEQ ID No. 83, total RNA RNAzol Bmethod (Tel-Test), and a cDNA synthesis kit (Promega). The followingprimers with indicated sequence positions were used in the reactions:

F1s GCAGACCTAAAGGAGCGTT 1 SEQ ID No.91 G7as CCCGACCATTGGAGAAGATA 1311SEQ ID No.92 G20s GCCAGTACCAGTGCCATGA 1054 SEQ ID No.93 G29asCCTCATGACACTGATACTCTT 2540 SEQ ID No.94 G26s GGCTGTGAGCAGGTCTGT 2109 SEQID No.95 G16as CGACCACTAATTGAATCAAAATC 4540 SEQ ID No.96 G16sCGGTGCTCGTGTGATACAG 4338 SEQ ID No.97 E2as ATCCACATCCACATGCAG 6413 SEQID No.98 E4s CCTCAAATGGCTGTAGCAACAA 6157 SEQ ID NO.99 B9asCTGCTGCTGCACGTGTGA 8704 SEQ ID No.100 B5s CCAGTCTGGATACACAAAATGT 8570SEQ ID No.101 23.5 GGCGCACTGCCATTC 10,910 SEQ ID No.102 G19sCTCAGATGGCTCTGATGAACT 10,718 SEQ ID No.103 G36as GCGTTTTCTCTTTCTTTCCTT13,026 SEQ ID No.104 G35s GAGAGTCATTGCAAAGGAAGCA 12,893 SEQ ID No.105G31as AATATATGTGCAAAAGTGTGTTT 14,120 SEQ ID No.106

Four separate reverse trancriptase (RT) reactions were performed usingthe following primers:

RT reaction 1 (RT1) primer G29as RT reaction 1 (RT2) primer E2as RTreaction 1 (RT3) primer 23.5 RT reaction 1 (RT4) primer G31as

The following primers were used for PCR with listed RT reaction:

primer RT reaction F1s/G7as RT1 G20s/G29as RT1 G26s/G16as RT2 G16s/E2asRT2 E4s/B9as RT3 B5s/23.5 RT3 G19s/G36as RT4 G35s/G31as RT4

PCR amplification of first-strand cDNA was performed in a Perkin-Elmer9600 Thermal Cycler using the following program: 1 cycle of denaturationat 94° C. for 2 min., followed by 40 cycles of denaturation at 94° C.for 15 sec., annealing at 51° C. for 10 sec., and extension at 72° C.for 3 min., after which, the products of the reactions were separated byelectrophoresis and gel purified (QIAGEN). PCR reagents were purchasedfrom Perkin- Elmer and used according to manufacturer's suggestions. PCRfragments were then nucleotide sequenced using a dideoxynucleotidechain-termination method (Perkin-Elmer Prism Dye Deoxy Terminator CycleSequencing Kit), and an ABI 373 automated DNA sequencer (AppliedBiosystems). PCR fragments from four separate reactions were sequencedon both strands to confirm sequence data. Computer generated DNAsequence analysis was performed using Auto-Assembler and Factura(Applied Biosystems), and MacVector and AssemblyLIGN (Eastman KodakCompany) software programs.

Database search. The EMBL-31 database in the Intelligenetics format(Intelligenetics Rel.5.4), was searched for sequence similarities to theplacental cDNA sequence using the FAST DB algorithm (13).

Immunostaining and Northern blot. Immunohistochemical studies wereperformed on acetone-fixed, 6 pm thick frozen sections, utilizing themonoclonal antiparathyroid antibodies E11 and G11, at concentrations of5 μg/ml, together with a mouse peroxidase antiperoxidase technique onhuman placental, parathyroid, kidney, and epididymis specimens as wellas on the other human tissues—see above (1,7). Monoclonal antibodies tocollagen-type II were used as negative controls (14).

Total RNA was extracted from tissue samples by the acidphenol/chloroform method. For Northern blot analysis approximately 10 μgof total RNA was electrophoresed in a 1.5%/37% agarose/formaldehyde gel,blotted onto nylon membranes (Qiabrane, Diagen GmbH, Dusseldorf,Germany) and probed with the 2.3 kb clone (see results) labeled by therandom priming method. Hybridizations were performed at 42° C. for 18-24h in 50% formamide, 4×saline sodium citrate (SSC; 300 mM NaCl, 30 mMNa-citrate, pH 7.0), 2×Denhart's solution, 10% dextran sulfate(Kabi-Pharmacia, Uppsala, Sweden) and 100 μg/ml salmon sperm DNA.Filters were washed at a final stringency of 1×SSC/0.1% SDS for 30 sinat 42° C., and exposed within a phosphorimager as above.

CAS Peptide Binding Analysis: A peptide corresponding to one putativeCAS SH3 binding region (ATPPPSPSLPAKPKPPSRR) (SEQ ID No. 18) wassynthesized on an ABI model 430A synthesizer using FastMoctm chemistry.The peptide was HPLC purified and analyzed by mass spectroscopy. 5 mg ofthe peptide was coupled to 500 ul of Amino Link (Pierce) agarose asdescribed by the supplier. Efficiency of coupling was checked by RP-HPLCof peptide solution before and after coupling and spectrophotometricallyat a wavelength of 220 nm. Both methods indicated a coupling efficiencyof >70%. The coupled peptide was reacted with 5 ug aliquots of variousGST-SH3 fusion proteins at room temperature for 1 hour before the resinwas washed extensively with TTBS. The resin was boiled in SDS loadingdye and electrophoresed on an SDS-PAGE gel. Binding ability of thevarious SH3 proteins for the peptide was judged by the relativeintensity of the Coomassie blue-stainable bands on the SDS gel. GSTprotein alone was used alone as a control.

Expression and Purification of GST-SH3 fusion Proteins: VariousGST-SH3-containing fusion clones were kind gifts from Dr. I. Gout,Ludwig Inst. for Cancer Research, London, UK. The fusion 25 proteinswere all produced by inducing their expression in XL1-blue E. coli using1 mM IPTG. Cells containing the fusion proteins were sonicated in PBScontaining 10 mM EDTA and 1% Triton-X 100. After pelleting cell debris,the cleared lysate was applied to a glutathione-Sepharose column(Pharmacia), and the bound fusion protein was eluted with 10 mM reducedglutathione in 50 mM Tris pH 8.0. These purified fusion proteins werethen dialyzed extensively against PBS before being used in allsubsequent experiments. Protein was quantified by measuring theabsorbance at 280 nm followed by characterization by SDS polyacrylamidegel electrophoresis.

RESULTS

Isolation of the calcium sensor protein, peptide cleavage and sequencedetermination.

The calcium sensor protein was purified from placental tissue by meansof Pectin chromatography, immunosorbent chromatography utilizing theimmobilized monoclonal anti-parathyroid antibodies, and finally ionexchange chromatography (1,7). The same antibodies were used in asandwich ELISA to monitor the purification (7). In order to avoidcontamination with low molecular peptides, the whole final preparation,consisting of 200 μg of the 500 kDa protein chain (7), was made 6 M withregard to guanidine-HCl and applied to a gel chromatography column,equilibrated with 2 M guanidine-HCl, 0.1 M Tris-Cl, pH 8.5. The columnwas eluted with the same buffer. Virtually all protein material emergedclose to the void volume at the expected position for a protein with amolecular mass of 500 kDa. Separate fractions containing this materialwere combined and endoproteinase Lys C (1 μg) was added. The digestionwas allowed to proceed over night at 37° C. The fragmented protein wasreduced by incubation with 0.1% β-mercaptoethanol at 37° C. for 30 minand subsequently alkylated with 4-vinyl pyridine (0.3%) at roomtemperature for 2 h. The peptide mixture was then applied to a reversedphase C₄ column equilibrated in 5% acetonitrile in 0.2% trifluoroaceticacid. Peptides were eluted by a linear gradient of 5-60% acetonitrile in0.02% trifluoracetic acid (FIG. 1). Due to the large number of peptides,the elution pattern was complex. Several peptide fractions weresequenced in a gas phase sequenator and easily interpretable sequenceswere obtained for two fractions (FIG. 2, SEQ ID Nos. 1 and 2).

Isolation of a cDNA clone encoding the 500 kDa calcium sensor.

An oligonucleotide mixture (48 bp) was constructed to encode amino acidresidues 2 to 17 of the sequenced peptide 292. To reduce the complexityof the oligonucleotide mixture, five inosine bases were inserted atdegenerated positions where no guidance could be obtained from the codonusage in humans. At nine positions, where two bases were possible, oneof the bases was suggested with a likelihood exceeding 70% from codonusage, and was therefore used in the oligonucleotide mixture.

The mixed oligonucleotide was radioactively labelled and used as a probeto screen a human placental λ gt 11 cDNA library. Approximately 2×10⁶plaques were screened and a single positive clone, CAS-1, was found. Theinsert of this clone was estimated to 2.3 kb, by restriction mapping. Toobtain a recognizable sequence of the clone in a rapid way, an attemptwas made to PCR amplify part of the sequence using degeneratedoliogonucleotides corresponding to part of peptides 292 and 293 asprimers. A distinct DNA fragment of approximately 430 bp was obtainedassuming that the peptide 292 is located carboxy-terminal to peptide293. The fragment was partially sequenced using the oligonucleotidemixture corresponding to peptide 293 as the primer. In one reading framefrom the obtained sequence, the sequence VGRHI could be deduced, inexcellent agreement with the carboxyterminal 5 amino residues of peptide293. To obtain a clone with a larger insert a human placental λ ZAP-IIcDNA library reported to contain clones with large inserts was screenedwith the PCR fragment as the probe. From 2×10⁶ plaques a single clone,CAS-2, was found. The insert of this clone, estimated to 2.8 kb, wasreleased in the Bluescript + vector, using a helper phage. Part of theinsert of this clone, pCAS-2, was sequenced using syntheticoligonucleotides as primers (FIG. 3, SEQ ID No. 3). An open readingframe was found containing both peptide 292 and 293. There was perfectagreement between the peptide sequences and the predicted amino acidsequence (SEQ ID No. 4) from the cDNA clone. The complete sequence ofthe 2.8 kb CAS-2 is shown in FIG. 6 (SEQ ID No. 11).

The CAS-2 sequence was extended using standard methodology. Reversetranscriptase PCR amplification and standard ³²P-labeled probe screeningof human lambda kidney cDNA libraries were used to complete the cloningof the CAS cDNA (SEQ ID No. 83). Probe fragments were designed offappropriate clones, starting with clone pCAS-2 (FIG. 11), to allowisolation of overlapping but 5′-extended clones from these libraries.This cDNA walking procedure was used for the isolation of all cDNAclones except clones pMeg2, pHP1C8, pHP1B1, and pM4B1. These clones wereisolated from human kidney cDNA libraries using rat gp330 PCR amplifiedprobe fragments (nts. 148-1249, 2892-3873, 4553-5693, and 5868-6968)obtained with rat cDNA prepared from rat kidney total RNA. Three smallcloning gaps (aa 564-997, 1622-1836, and 2212-2312;) were completed bydirect PCR amplification through these regions using specific humangp330 oligonucleotide primers and cDNA prepared from human kidney totalRNA (CAS-1750, -1210, and -700).

An extended calcium sensor sequence is shown in SEQ ID No. 17. Acomplete human calcium sensor sequence in shown in SEQ ID Nos. 83 and84. Based on the above cloning procedure amino acids 1-3711 of SEQ IDNo. 84 were determined from human kidney cDNA whereas amino acids3712-4655 were identified from the CAS-2 placental cDNA clone (FIG. 11).

Full-length human placental (SEQ ID Nos. 85 and 86), kidney (SEQ ID Nos.87 and 88) and parathyroid (SEQ ID Nos. 89 and 90) CAS cDNA and aminoacid sequences have been determined by sequencing PCR fragments fromspecifically primed first-strand human placental, kidney and parathyroidcDNA, prepared using oligonucleotide primers designed off SEQ ID No. 83,total RNA RNAzol B method, and a cDNA synthesis kit as described inMaterial and Methods.

Comparison of all CAS sequences obtained so far reveals only fourpotential differences throughout the complete amino acid sequence:Alal²⁸⁷ to Ala/Pro, Ala²⁸⁷² to Thr, Lys⁴⁰⁹⁴ to Lys/Glu, and Ile⁴²¹⁰ toIle/Leu (FIG. 12). The ambiguous positions and the minor amino aciddifferences are most likely associated with normal ethnic and/or allelicvariation differences being reflected in the cDNA sources used inconstructing the cDNA libraries.

The 500 kDa placental calcium sensor belongs to the LDL-receptorsuperfamily.

A search in a database with the predicted amino acid sequence from FIG.3 (SEQ ID No 3) revealed that the placental 500 kDa protein ishomologous to receptors belonging to the LDL-receptor superfamily. Thehighest similarity was found with the rat Heymann nephritis antigen (11,67). FIG. 4 shows an alignment of placental 500 kDa protein sequence tothe sequence of the Heymann antigen (SEQ ID No. 5) as well as to twoother members of the same protein superfamily, the LDL-receptor (SEQ IDNo. 6) and the LDLreceptor-related protein (identical to theα₂-acroglobulin receptor, (11,15,16), SEQ ID No. 7). The sequenceidentity between the placental calcium-sensor and the Heymann antigengp330 was estimated to be 82% in the region of comparison (236 aminoacid residues). A complete sequence of the human calcium sensor proteinis shown in SEQ ID No. 83. Overall, the identity between rat gp330 andthe human homolog is 77%. The structure of human gp330 is shown in FIG.10. The protein is 4655 amino acids in length and comprises anN-terminal signal peptide of 25 amino acids, a 4398 amino acidextracellular domain, a transmembrane region of 23 amino acids and aC-terminal domain of 209 amino acids. As shown in FIG. 10, the structureof human gp330 closely correlates with that of the rat homolog (FIG. 3of ref. 67).

Immunohistochemistry and Northern blot.

The close similarity between the placental 500 kDa calcium-sensorprotein and the rat Heymann nephritis antigen prompted the expandedimmunohistochemical investigation of the present study. Theantiparathyroid antibodies (E11 and G11) were found to stain not onlyparathyroid, placental and proximal kidney tubule cells but alsoepididymal cells, as previously demonstrated for antibodies reactivewith the Heymann antigen (17-20).

Northern blot analysis of total RNA (approximately 10 μg/lane) fromhuman kidney, placenta and parathyroid glands with the identified 2.8 kbclone as the probe, revealed one major hybridizing RNA species ofapproximately 15,000 bases in all these tissues (FIG. 5). Human liver,pancreas, adrenal gland, and small gut (FIG. 5) as well as spleen, lungand striated muscle (not shown) lacked hybridizing species.

Identification of SH2 and SH3 binding regions in the cytoplasmic domainof the calcium sensor:

Src-homology regions 2 and 3 (SH2 and SH3) are conserved sequence motifsconsisting of approximately 100 and 60 amino acid residues,respectively, and are found in many eukaryotic proteins with diversefunction (42-44). SH3 domains have been identified in severalcytoskeleton-associated proteins, such as p80/p85, myosinlb, spectrin,neutrophil NADPH oxidase-associated proteins p47 and p67, and in severalyeast proteins important for morphogenesis (i.e., Bemlp and ABP-1),mating (FUS1) or for regulation of ras activity (cdc25 and ste6 (forreview see Mussachio et al. (45)). The observation that manySH3-containing proteins are cytoskeleton-associated led to thesuggestion that SH3 domains play a role in multimeric protein complexformation at or near cytoplasmic membranes. Some proteins that containboth SH2 and SH3 domains perform the function of adaptor molecules byjoining activated receptor tyrosine kinases with p21 ras guaninenucleotide-releasing protein (GNRP). For example, Grb2 and itshomologues bind to phosphotyrosine on activated membrane-anchoredreceptor tyrosine kinases through their SH2 domain and to SOS throughtheir amino-and carboxyterminal SH3 domains (46-50). These processeslead to translocation of SOS to the plasma membrane where ras proteinsare interacted with and consequently activated. Thus, SH2/SH3-containingand SH2/SH3-binding proteins are involved in a highly conserved signaltransduction pathways from activated receptors.

Complete nucleic acid sequencing and translation of the 2.8 kb humancDNA clone CAS-2 (FIG. 6) (SEQ ID Nos. 11 and 12) demonstrate theexistence of at least three potential SH3 binding regions denoted asCAS-PEP1 (SEQ ID No. 14), CAS-PEP2 (SEQ ID No. 15), and CAS-PEP3 (SEQ IDNo. 16) (FIG. 7). All three of these CAS-2 cytoplasmic peptide regionshave the required consensus sequence of a SH3-binding region, which isshown together with the CAS peptides in FIG. 7 (53). Further supportthat the cytoplasmic domain of CAS-2 binds SH3 regions is shown in theevidence in FIG. 8. A region of the CAS-2 cytoplasmic domain(ATPPPSPSLPAKPKPPSRR) (SEQ ID No. 18) that included CAS-PEP1 (PSLPAKP,FIG. 7) was synthesized. The peptide was incubated with various purifiedGST-SH3 fusion proteins and the relative binding strengths of the fusionproteins was assayed by SDS-PAGE (FIG. 8). The data clearly indicatethat several of the SH3-region containing proteins had an affinity forthe peptide containing CAS-PEP1, with the following relative order ofdecreasing affinities: LANE 6: SH3-PI3K (SH3 of p85 subunit ofphosphoinositol-3 kinase, (54,55))>LANE 7: SH3-PLC-gamma,(phospholipase-C gamma, (56))>LANE 2: SH3-FYN (src-family solubletyrosine kinase, (57),>LANE 4: SH3-GRB2, (growth factor receptor bindingprotein N-terminal SH3) and LANE 5 (C-terminal SH3 of GRB2) (58,59).

Significantly, all of the positive reacting SH3-containing proteinsshown in FIG. 8 are intimately associated with signal transduction andstimulation of cell growth (54-59). PI3K contains two SH2 regions andone SH3 region. PI3K is relatively new to the family of signaltransducing molecules, but appears to be involved with insulin signalingthrough the glucose transporter, and is believed to associate directlywith the ras protein. PLC-gamma is a well known signaling molecule alsocontaining two SH2 regions and one SH3 region, and is known to hydrolyzemembrane lipids to other powerful downstream signaling molecules (eg.IP3 and diacylglycerol) when stimulated by ligand activated growthfactor receptors. FYN is a highly characterized member of the src-familyof soluble tyrosine kinases known to be intimately associated with cellgrowth and differentiation. FYN contains one SH2 and one SH3 region, isalso known to be stimulated by ligand activated growth factor receptors.GRB2 contains two SH3 regions and one SH2 region, and is known as anadaptor molecule in that it has no known intrinsic enzymaticcapabilities. GRB2 molecules are also stimulated by ligand activatedgrowth factor receptors. It is also worth noting that SH3-GAP (GTP-aseactivating protein, LANE 3, (60, 61)), and SH3-NCF (neutrophil cytotoxicfactor-type 1, LANE 8, or -type 2, lane 9, (62, 63)) had little or noaffinity for the peptide containing CAS-PEP1. This evidence supports thespecificity of the interaction between the CAS-PEP1 and various SH3domains. In addition, CAS-PEP1 does not bind a control GST fusionprotein as shown in lane 1 of FIG. 8.

The cytoplasmic domain of CAS-2 also comprises a p85-SH2 binding region.Though different SH2 containing proteins all require phosphorylatedtyrosine residues for an interaction, it is well established that theamino acid residues surrounding the tyrosine residue dictate thespecificity and strength of the interaction (64). FIG. 9 defines thoseamino acid sequence requirements that are necessary for interaction withthe SH2 region of the p85 regulatory subunit of PI3K. The evidenceclearly shows that for a binding interaction to take place with the SH2region of p85, the tyrosine residue must be included in the amino acidsequence motif YXXM (where “X” can be any amino acid), and must have anacidic amino acid residue (D or E) approximately 3-5 residues in eitherdirection of the YXXM motif. This exact amino acid sequence requirementexists in the cytoplasmic domain of CAS-2 (FENPIYAQMENE) (SEQ ID No.19), and is underlined in the CAS-2 cytoplasmic sequences at the top ofFIG. 9.

Altogether, the evidence demonstrates that the cytoplasmic domain of thecalcium sensor protein of the invention contains three consensus SH3binding regions and one potential SH2 recognition region of the typerecognized by the SH2 region of p85 and supports an involvment of SH2and SH3 mediated signal transduction for biological activity of thecalcium sensor protein, possibly through PI3K. The potential interactionof PI3K with the calcium sensor protein is even more interesting inlight of recent evidence linking the CAS-2 protein to calcium sensing inhuman parathyroid tissue, given that calcium sensing appears to involveG-protein activation, PKC activation, and inositol phosphate generation,all of which are activities that can be associated with PI3K signaltransduction cascades. Therefore, these regions provide useful tools inassays for the identification of compounds that either stimulate orinhibit the signal transduction pathways used by the calcium sensorprotein. Using assay techniques known to those skilled in the art,agonists or antagonists which mimic or inhibit the activity of thecalcium sensor protein SH2/SH3 regions will be useful for the treatmentof diseases that are intimately associated with the sensor, such asprimary hyperparathyroidism (HPT) (52) and osteoporosis.

The relation of the calcium sensor protein to the LDL-receptorsuperfamily of proteins was noted above. All of the members of theLDL-receptor superfamily are “scavenger” proteins. None of thesescavenger proteins have recognized signal transduction regions, andspecifically, none of these scavenger proteins contain SH regions.Therefore it was entirely unexpected to identify SH2 and SH3 bindingregions active in signal transduction in the calcium sensor protein. Theoccurrence of these regions is a further indication that the calciumsensor protein is not a scavenger protein, even though it has regions ofhomology with the LDL-receptor superfamily of scavenger proteins.

Rat Heymann nephritis antigen, gp330, belongs to the LDL receptorsuperfamily of large, multifunctional glycoproteins (68, 69, 70).Identification of the calcium sensor protein as the human homolog of ratgp330 enables new diagnostic and therapeutic agents for human disease.

Examples of diagnostic and therapeutic uses for gp330, or biologicallyactive fragments thereof, are disclosed in EP 358,977, the entirecontents of which are incorporated herein by reference. For example,human gp330, or fragment thereof, may be used in assays for detectingautoantibodies associated with human membranous glomerulonephritis.Examples of suitable assays include immunoassays, such as ELISA.Alternatively, synthetic peptides based on the human gp330 sequence maybe used to localize immunodominent B- or T-lymphocyte recognition sites.Therefore, the invention enables detection of gp330 specificautoantibodies and helper, cytotoxic or suppressor T-cells. Theinvention permits identification of patients who may develop idiopathicautoimmune membranous glomerulonephritis and patients susceptible toautoimmune membranous glomerulonephritis following a renal allograft.

Human gp330 is useful for treatment of human membranousglomerulonephritis according to a variety of methods, For example, gp330may be coupled to a polyphenol followed by immunization of a patientaccording to U.S. Pat. No. 4,702,907, the entire contents of which areincorporated herein by reference. Treatment in this manner results inselective immunosupression of antibodies specific for gp330. As analternative method of treatment, it is also possible to selectivelyremove gp330-reactive autoantibodies from sera by immobilizing gp330, orfragment thereof, on a solid support and pass the sera over the support,thereby effectively removing autoantibodies characteristic of humanmembranous glomerulonephritis. Alternatively, human gp330, or a fragmentthereof, can be directly administered to a patient in order to perturbformation of immune complexes. Synthetic peptides based on the sequenceof human gp330 are also useful therapetically. Administration ofimmunogenic peptides inhibits activation or function of gp330 specifichelper and cytotoxic T-cells.

The structure of human gp330 includes 16 growth factor repeats separatedby 8 YWTD spacer regions and 1 epidermal growth factor repeat in theimmediate extracellular juxtamembrane region (FIG. 11). Therefore,administration of gp330, or a fragment thereof having growth factoractivity, is useful in the treatment of wounds, such as burns andabrasions. Epidermal growth factor is also a potent inhibitor of gastricacid secretion. Therefore, gp330, or a fragment thereof having epidermalgrowth factor activity, is useful for treatment or prevention of gastriculcers. Determination of effective amounts of therapeutic agent foradministration is within the skill of the practitioner.

A further object of this invention is a method for treating disorders ofthe central nervous system characterized by amyloid beta proteinaccumulation. Human gp330 mediates the cellular uptake and transport ofamyloid beta protein at the blood-brain barrier and blood cerebrospinalfluid barriers (71). This process is inhibited by proteins capable ofbinding gp330. Selective inhibition of gp330 expression or function incells at the cerebrovascular endothelium and/or choroid epithelium willserve to slow or halt the accumulation of amyloid beta protein, such asin senile plaques, a hallmark of Alzheimer disease. This inventionprovides several embodiments for specifically inhibiting gp330 activityat selected tissues in a patient suffering from abnormal amyloid betaprotein accumulation.

As a first embodiment, gp330 expression is inhibited by nucleic acidscomprising a sequence complementary to the sequence encoding human gp330and down-regulating or blocking expression of gp330. A preferredembodiment comprises an antisense polynucleotide molecule. Preparationand use of antisense polynucleotides, DNA encoding antisense RNAmolecules and use of oligo and genetic antisense is disclosed in WO92/15680, the entire contents of which are incorporated herein byreference.

Antisense nucleic acids of the invention are preferably RNA capable ofspecifically hybridizing with all or part of the sequence selected fromthe group consisting of SEQ ID No. 3, SEQ ID No. 11, SEQ ID No. 83, SEQID No. 85, SEQ ID No. 87, and SEQ ID No. 89 or the correspondingmessenger RNA. The antisense sequence of the present invention may bederived from DNA sequences whose expression in the cell produces RNAcomplementary to all or part of human gp330 mRNA. These antisensesequences can be prepared by expression of all or part of the sequenceselected from the group consisting of SEQ ID No. 3, SEQ ID No. 11, SEQID No. 83, SEQ ID No. 85, SEQ ID No. 87, and SEQ ID No. 89 in theopposite orientation (EP 140 308). Any length of the antisense sequenceis suitable for practice of the invention so long as it is capable ofdown-regulating or blocking expression of gp330. Preferably, theantisense sequence is at least 20 nucleotides in length.

In another aspect of this preferred embodiment the nucleic acid encodesantisense RNA molecules. In this embodiment, the nucleic acid isoperably linked to signals enabling expression of the nucleic acidsequence and is introduced into a cell utilizing, preferably,recombinant vector constructs, which will express the antisense nucleicacid once the vector is introduced into the cell. Examples of suitablevectors includes plasmids, adenoviruses, adeno-associated viruses,retroviruses, and herpes viruses. Preferably, the vector is anadenovirus. Most preferably, the vector is a replication defectiveadenovirus comprising a deletion in the E1 and/or E3 regions of thevirus. Examples of viruses capable of infecting cells of the centralnervous system are disclosed in WO 94/08026, the entire contents ofwhich are incorporated herein by reference.

Suitable expression signals include transcriptional promoter andtermination sequences. Among the promoter sequences useful for practiceof this invention are tetracycline-regulated transcriptional modulatorsand CMV, SV-40, E1a, MLP, and LTR promoters. Tetracycline-regulatedtranscriptional modulators and CMV promoters are described in WO96/01313, U.S. Pat. No. 5,168,062 and 5,385,839, the entire contents ofwhich are incorporated herein by reference.

The nucleic acid constructs of this invention are capable ofdown-regulating or blocking expression of human gp330, and aredelivered, in a preferred aspect of the invention, locally to cells ofthe central nervous system. Alternatively, the nucleic acid is deliveredstereotaxically to specific sites in the brain. WO 94/08026 disclosesmethods for localized delivery of replication defective adenoviruses tospecific cells of the central nervous system, including stereotaxicdelivery to sites in the brain.

A second embodiment of the present invention's method of specificallyinhibiting human gp330 activity at selected sites, comprises inhibitinggp330 function by expression of a nucleic acid sequence encoding anintracellular binding protein capable of selectively interacting withgp330 within a transfected cell. WO 94/29446 and WO 94/02610, the entirecontents of which are incorporated herein by reference, disclosecellular transfection with genes encoding an intracellular bindingprotein. An intracellular binding protein includes any protein capableof selectively interacting, or binding, with human gp330 in the cell inwhich it is expressed and of neutralizing the function of bound humangp330. Preferably, the intracellular binding protein is an antibody or afragment of an antibody. More preferably, the antibody or fragmentthereof binds the cytoplasmic domain of gp330. Most preferably, theintracellular binding protein is a single chain antibody capable ofinhibiting cellular uptake and transport of amyloid beta protein at theblood-brain barrier and blood cerebrospinal fluid barriers by bindingthe cytoplasmic domain of gp330.

WO 94/02610 discloses preparation of antibodies and identification ofthe nucleic acid encoding a particular antibody. Using gp330 or afragment thereof, a monoclonal antibody specific for the cytoplasmicdomain is prepared by according to techniques known to those skilled inthe art. A vector comprising the nucleic acid encoding an intracellularbinding protein, or a portion thereof, and capable of expression in ahost cell is subsequently prepared for use in the method of thisinvention. Suitable vectors and methods of delivering nucleic acidsencoding intracellular binding proteins to cells containing gp330include those discussed above for delivery of antisense nucleic acids.

In a preferred aspect of this second embodiment, the nucleic acidsequence encoding a gp330 intracellular binding protein additionallycomprises a sequence encoding a localization signal for targeting theintracellular binding protein to the cellular location of gp330 and/or asequence enabling insertion of the intracellular binding protein in theplasma membrane. The localization signal or insertion sequence can belocated anywhere on the intracellular binding protein, so long as itdoes not interfere with binding to gp330. Examples of localizationsignals are disclosed in WO 94/02610. Preferably, the localizationsignal targets the intracellular binding protein to the plasma membrane.

Discussion

The important role of the parathyroid as key regulator of the calciumhomeostasis has been related to its exquisite capacity to sense andrespond to variation in the extracellular Ca²⁺ ion concentration.Essential for recognition of changes in external calcium is a cationreceptor or sensor of the parathyroid cell membrane, the presence ofwhich was implicated by a series of in vitro studies on parathyroid cellregulation (9, 10, 21-24). The concept of a cell membrane receptor wasfurther substantiated when monoclinal antiparathyroid antibodies werefound to recognize and interfere with the calcium sensing of parathyroidcells (1-6). Another crucial piece of evidence was obtained whencytotrophoblast cells of the human placenta, selected by theirreactivity with the antiparathyroid antibodies, displayedparathyroid-like sensing of changes in external calcium, a functionwhich also could be blocked by one of the anti-parathyroid antibodies(7,8). The calcium sensor of the placenta was subsequently isolated byimmunosorbent and ion exchange chromatographies and shown to consist ofa large glycoprotein of approximately 500 kDa molecular size (7). It wasalso demonstrated by irmunoprecipitation that a protein of the same sizereacted with the antiparathyroid antibodies within the parathyroid andkidney tubule cells (to be published, (25).

The parathyroid calcium sensor or receptor is known to have features incommon with most other classical receptors for cellular activation,although it exhibits the unusual ability to bind and be activated bydivalent cations. Cation binding triggers biphasic rise in [Ca²⁺i] andconcomittant activation of phospholipase C, possibly via a coupledG-protein, with a resulting accumulation of inositol phosphates(2,5,9,10). An initial transient rise in [Ca²⁺i] is due toinositoltrisphosphate (Ip3)induced mobilization of Ca²⁺ fromintracellular sources, while an ensuing steady-state elevation in[Ca²⁺i] is caused by calcium gating through plasma membrane channels,possibly mediated by increase in inositol-tetraphosphate (Ip4)(9,10,23).

Sequence analysis of a partial cDNA clone and data-base comparison ofthe deduced amino acid sequence showed that the placental calcium sensorprotein belongs to the LDL-receptor superfamily of proteins, andavailable sequences showed close similarity with the rat Heymannnephritis antigen (11,15,16). This antigen was originally described inthe rat as a 330 kDa glycoprotein (gp 330), present within the proximalkidney tubule brush border, and in placental and epididymal cells, butby special staining techniques also demonstrated to occur sparsely onrat kidney glomerular cells, as well as on pneumocytes II in the lungand sporadic cells of the liver and small intestine (17-19). It haslater been proposed that the molecular size of the protein wasunderestimated and actually should be in the range of 500 kDa (20). TheHeymann antigen has been revealed as the dominating antigen causingmembranous, autoimmune glomerulonephritis in the rat after immunizationwith a crude tubular protein fraction (17,19). Using anti-gp 330antibodies a protein with an estimated molecular size larger than 400kDa has been identified in man (20). The sequence identity of 77%between the human placental 500 kDa calcium sensor protein and the ratHeymann nephritis antigen indicates that they represent related forms ofthe calcium sensor protein in two different species. This view issupported by close similarities in tissue distribution of the twoproteins, as revealed by the immunohistochemistry of the present study.The antibodies E11 and G11, reacting with the calcium sensor protein,thus stain parathyroid cells, proximal kidney tubule cells, placentalcytotrophoblasts and also epididymal cells. Furthermore, we haverecently reported staining with one of the antiparathyroid antibodiespreferentially within coated pits and the base of the proximal tubulemicrovilli, which equals that previously described with antibodiesagainst the gp 330 protein (19,26). A recognized glycoprotein of similarsize within the tubule brush border, renal maltase, has been locatedmainly to microvillar membranes and not within the coated invaginations(18).

Thus far recognized members of the LDL-receptor superfamily, theLDL-receptor, the LDL-receptor-related protein and the Heymann antigen,have been thought to function as receptors for proteins, but all exhibitfunctionally important Ca²⁺-binding ability (16,27,28). Thus, Ca²⁺binding is necessary for the interaction of the LDL-receptor with apo-B(27). The LDL-receptor related protein (α₂-macroglobulin receptor) isalso known to bind Ca²⁺, which induces conformational changes, and Ca²⁺is necessary for binding of activated α₂-macroglobulin to the receptor(16). Recently, the rat Heymann antigen was shown by a blottingtechnique to interact with Ca²⁺ (28).

The Ca²⁺ binding motifs of the calcium sensor protein remain to beidentified. The sensor protein (as well as the Heymann antigen) containsEGF-like modules, like other members of the LDL-receptor superfamily(11,16,27), which may represent putative Ca²⁺ binding sites. Thus, whenpresent in the coagulation factors IX, X and protein C, each EGF-likemodule is known to bind one Ca²⁺ ion (29-34), and the EGF-like moduleshave also been demonstrated to mediate Ca²⁺ dependent protein/proteininteraction (35). Kinetic data have suggested that the calcium sensordisplays positive cooperativity in its interaction with Ca²⁺, aphenomenon which appears essential for the sigmoidal regulation of[Ca²⁺i] and PTH release, with a steep relation within the physiologicalrange of extracellular calcium (9,10). The positive cooperativity shouldrequire multiple binding sites for Ca²⁺, possibly resulting from therepetitive EGF-like modules, generally present in molecules of theLDL-receptor superfamily (11,16,27). However, Ca²⁺ binding to EGF-likedomains are known to induce only minor, localized pertubations of thethree-dimensional structure (32), and it is possible that the calciumsensor contains also other Ca²⁺ binding sites.

A 43 kDa membrane protein (α₂-macroglobulin receptor-associated protein,or Heparin-binding protein) (28,36) is known to interact both with theLDL-receptor-related protein and with the rat Heymann antigen in a Ca²⁺dependent manner (28). No physiological function has yet been assignedto this protein, but it appears also in tissues where the Heymannantigen and the LDL-receptorrelated proteins are not expressed (28). Anintriguing observation is the presence of a putative leucine-zippermotif in the aminoterminal part of the 43 kDa protein (36), consideringthat such motifs have been suggested to influence the opening andclosure of membrane ion channels (37). Since the 43 kDa proteininteracts with the Heymann antigen, it can be assumed to form a complexalso with the calcium sensor protein in a Ca²⁺⁻ dependent manner.Interaction with the 43 kDa protein might be important for thetransmission of Ca²⁺ induced conformational changes within theextracellular portion of the molecule to the cell interior. It is alsopossible that additional proteins interact with the calcium sensor in aCa²⁺ dependent manner, and that such an interaction is important for themodulation of the sensor response. The mechanisms by which an activatedcalcium sensor triggers further signalling to the cell interior isunknown, although we have in preliminary experiments utilizedimmunoprecipitation to isolate a phosphorylated form of the sensorprotein in dispersed parathyroid cells loaded with [³²p]-orthophosphate(unpublished observation).

The calcium sensor protein of the placenta may be involved inmaintenance of a feto-maternal Ca²⁺ gradient and placental Ca²⁺transport, possibly by mediating calcium regulation of the parathyroidhormone related peptide (PTHrP) production and/or 1,25 (OH)₂D₃metabolism (8). Its presence already within the blastocyst (unpublishedobservation) may indicate a function also as adhesion molecule, orimplicate involvement in differentiation or growth regulation, assuggested for the Heymann antigen (38). The function of a calcium sensorwithin the kidney tubule brush border is less well explored. However, itshould be noted that the enzyme 1-α-hydroxylase present in the placentaand proximal kidney tubule, is regulated by extracellular calcium, andthe calcium sensor might accordingly regulate 1,25 (OH)₂D₃ metabolism,but it may possibly also influence Ca²⁺ reabsorption from the glomerularfiltrate (7-9). The significance of the presence of the calcium sensorprotein on epididymal cells, as well as rat pneumocytes, liver andintestinal cells as implicated by the distribution of the Heymannantigen (18,19), yet remains unknown. It has, however, been proposedthat several cell types may exhibit Ca²⁺ sensing ability for regulationof various functions, separate from the general calcium homeostasis,either during development or in the differentiated state (10).

The association with autoimmune nephritis substantiates that the Heymannantigen is an immunogen molecule. This may have implication also inparathyroid disorder, as we have recently reported the presence ofcirculating parathyroid autoantibodies and induction of class IItransplantation antigen in the pathological parathyroid tissue ofpatients with primary HPT. These findings suggested that autoimmunephenomena may be involved in HPT (39) and autoimmunity has also beenimplicated in the pathogenesis of rare idiopathic hypoparathyroidism(10). The availability of cDNA clones for the calcium sensor should,enable extended studies on the pathophysiology in parathyroid disorder,and also in vestigation of a possible genetic abberration affecting thecalcium sensing function of the parathyroid and kidney tubule inkindreds with familial hypocalciuric hypercalcemia (FHH) (40,41).

The skilled person within this art realizes that the informationobtainable from the nucleotide sequences of SEQ ID No. 3, SEQ ID No. 11,SEQ ID No. 83, SEQ ID No. 85, SEQ ID No. 87, and SEQ ID No. 89 can beused for isolating the genomic sequence encoding the calcium sensor.Preferably, an analysis of overlapping cDNA clones in conjunction withPCR techniques is used. The genomic sequence can be obtained from theanalysis of overlapping genomic cosmid and/or lambda phage clones.

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106 17 amino acids amino acid linear peptide internal unknown 1 Xaa AlaMet Asn Pro Tyr Ser Leu Asp Ile Phe Glu Asp Gln Leu Tyr 1 5 10 15 Trp 13amino acids amino acid linear peptide internal unknown 2 Xaa Val Met GlnPro Asp Gly Ile Ala Xaa Asp Trp Val 1 5 10 804 base pairs nucleic aciddouble linear cDNA unknown CDS 1..804 3 AAA TAC GTA ATG CAG CCA GAT GGAATA GCA GTG GAC TGG GTT GGA AGG 48 Lys Tyr Val Met Gln Pro Asp Gly IleAla Val Asp Trp Val Gly Arg 1 5 10 15 CAT ATT TAC TGG TCA GAT GTC AAGAAT AAA CGC ATT GAG GTG GCT AAA 96 His Ile Tyr Trp Ser Asp Val Lys AsnLys Arg Ile Glu Val Ala Lys 20 25 30 CTT GAT GGA AGG TAC AGA AAG TGG CTGATT TCC ACT GAC CTG GAC CAA 144 Leu Asp Gly Arg Tyr Arg Lys Trp Leu IleSer Thr Asp Leu Asp Gln 35 40 45 CCA GCT GCT ATT GCT GTG AAT CCC AAA CTAGGG CTT ATG TTC TGG ACT 192 Pro Ala Ala Ile Ala Val Asn Pro Lys Leu GlyLeu Met Phe Trp Thr 50 55 60 GAC TGG GGA AAG GAA CCT AAA ATC GAG TCT GCCTGG ATG AAT GGA GAG 240 Asp Trp Gly Lys Glu Pro Lys Ile Glu Ser Ala TrpMet Asn Gly Glu 65 70 75 80 GAC CGC AAC ATC CTG GTT TTC GAG GAC CTT GGTTGG CCA ACT GGC CTT 288 Asp Arg Asn Ile Leu Val Phe Glu Asp Leu Gly TrpPro Thr Gly Leu 85 90 95 TCT ATC GAT TAT TTG AAC AAT GAC CGA ATC TAC TGGAGT GAC TTC AAG 336 Ser Ile Asp Tyr Leu Asn Asn Asp Arg Ile Tyr Trp SerAsp Phe Lys 100 105 110 GAG GAC GTT ATT GAA ACC ATA AAA TAT GAT GGG ACTGAT AGG AGA GTC 384 Glu Asp Val Ile Glu Thr Ile Lys Tyr Asp Gly Thr AspArg Arg Val 115 120 125 ATT GCA AAG GAA GCA ATG AAC CCT TAC AGC CTG GACATC TTT GAA GAC 432 Ile Ala Lys Glu Ala Met Asn Pro Tyr Ser Leu Asp IlePhe Glu Asp 130 135 140 CAG TTA TAC TGG ATA TCT AAG GAA AAG GGA GAA GTATGG AAA CAA AAT 480 Gln Leu Tyr Trp Ile Ser Lys Glu Lys Gly Glu Val TrpLys Gln Asn 145 150 155 160 AAA TTT GGG CAA GGA AAG AAA GAG AAA ACG CTGGTA GTG AAC CCT TGG 528 Lys Phe Gly Gln Gly Lys Lys Glu Lys Thr Leu ValVal Asn Pro Trp 165 170 175 CTC ACT CAA GTT CGA ATC TTT CAT CAA CTC AGATAC AAT AAG TCA GTG 576 Leu Thr Gln Val Arg Ile Phe His Gln Leu Arg TyrAsn Lys Ser Val 180 185 190 CCC AAC CTT TGC AAA CAG ATC TGC AGC CAC CTCTGC CTT CTG AGA CCT 624 Pro Asn Leu Cys Lys Gln Ile Cys Ser His Leu CysLeu Leu Arg Pro 195 200 205 GGA GGA TAC AGC TGT GCC TGT CCC CAA GGC TCCAGC TTT ATA GAG GGG 672 Gly Gly Tyr Ser Cys Ala Cys Pro Gln Gly Ser SerPhe Ile Glu Gly 210 215 220 AGC ACC ACT GAG TGT GAT GCA GCC ATC GAA CTGCCT ATC AAC CTG CCC 720 Ser Thr Thr Glu Cys Asp Ala Ala Ile Glu Leu ProIle Asn Leu Pro 225 230 235 240 CCC CCA TGC AGG TGC ATG CAC GGA GGA AATTGC TAT TTT GAT GAG ACT 768 Pro Pro Cys Arg Cys Met His Gly Gly Asn CysTyr Phe Asp Glu Thr 245 250 255 GAC CTC CCC AAA TGC AAG TGT CCT AGC GGCTAC ACC 804 Asp Leu Pro Lys Cys Lys Cys Pro Ser Gly Tyr Thr 260 265 268amino acids amino acid linear protein unknown 4 Lys Tyr Val Met Gln ProAsp Gly Ile Ala Val Asp Trp Val Gly Arg 1 5 10 15 His Ile Tyr Trp SerAsp Val Lys Asn Lys Arg Ile Glu Val Ala Lys 20 25 30 Leu Asp Gly Arg TyrArg Lys Trp Leu Ile Ser Thr Asp Leu Asp Gln 35 40 45 Pro Ala Ala Ile AlaVal Asn Pro Lys Leu Gly Leu Met Phe Trp Thr 50 55 60 Asp Trp Gly Lys GluPro Lys Ile Glu Ser Ala Trp Met Asn Gly Glu 65 70 75 80 Asp Arg Asn IleLeu Val Phe Glu Asp Leu Gly Trp Pro Thr Gly Leu 85 90 95 Ser Ile Asp TyrLeu Asn Asn Asp Arg Ile Tyr Trp Ser Asp Phe Lys 100 105 110 Glu Asp ValIle Glu Thr Ile Lys Tyr Asp Gly Thr Asp Arg Arg Val 115 120 125 Ile AlaLys Glu Ala Met Asn Pro Tyr Ser Leu Asp Ile Phe Glu Asp 130 135 140 GlnLeu Tyr Trp Ile Ser Lys Glu Lys Gly Glu Val Trp Lys Gln Asn 145 150 155160 Lys Phe Gly Gln Gly Lys Lys Glu Lys Thr Leu Val Val Asn Pro Trp 165170 175 Leu Thr Gln Val Arg Ile Phe His Gln Leu Arg Tyr Asn Lys Ser Val180 185 190 Pro Asn Leu Cys Lys Gln Ile Cys Ser His Leu Cys Leu Leu ArgPro 195 200 205 Gly Gly Tyr Ser Cys Ala Cys Pro Gln Gly Ser Ser Phe IleGlu Gly 210 215 220 Ser Thr Thr Glu Cys Asp Ala Ala Ile Glu Leu Pro IleAsn Leu Pro 225 230 235 240 Pro Pro Cys Arg Cys Met His Gly Gly Asn CysTyr Phe Asp Glu Thr 245 250 255 Asp Leu Pro Lys Cys Lys Cys Pro Ser GlyTyr Thr 260 265 269 amino acids amino acid linear protein unknown 5 XaaXaa Xaa Xaa Xaa Pro Asp Gly Leu Ala Val Asp Trp Val Gly Arg 1 5 10 15His Ile Tyr Trp Ser Asp Ala Asn Ser Gln Arg Ile Glu Val Ala Thr 20 25 30Leu Asp Gly Arg Tyr Arg Lys Trp Leu Ile Thr Thr Gln Leu Asp Gln 35 40 45Pro Ala Ala Ile Ala Val Asn Pro Lys Leu Gly Leu Met Phe Trp Thr 50 55 60Asp Gln Gly Lys Gln Pro Lys Ile Glu Ser Ala Trp Met Asn Gly Glu 65 70 7580 His Arg Ser Val Leu Val Ser Glu Asn Leu Gly Trp Pro Asn Gly Leu 85 9095 Ser Ile Asp Tyr Leu Asn Asp Asp Arg Val Tyr Trp Ser Asp Ser Lys 100105 110 Glu Asp Val Ile Glu Ala Ile Lys Tyr Asp Gly Thr Asp Arg Arg Leu115 120 125 Ile Ile Asn Glu Ala Met Lys Pro Phe Ser Leu Asp Ile Phe GluAsp 130 135 140 Lys Leu Tyr Trp Val Ala Xaa Xaa Xaa Xaa Xaa Xaa Xaa XaaArg Gln 145 150 155 160 Asn Lys Phe Gly Lys Glu Asn Lys Glu Lys Val LeuVal Val Asn Pro 165 170 175 Trp Leu Thr Gln Val Arg Xaa Xaa Xaa Xaa XaaXaa Xaa Xaa Xaa Xaa 180 185 190 Xaa Xaa Xaa Xaa Cys Lys Gln Val Cys SerHis Leu Cys Leu Leu Arg 195 200 205 Pro Gly Gly Tyr Ser Cys Ala Cys ProGln Gly Ser Asp Phe Val Thr 210 215 220 Gly Ser Thr Val Gln Cys Xaa XaaXaa Xaa Xaa Xaa Pro Val Thr Met 225 230 235 240 Pro Pro Pro Cys Arg CysMet His Gly Gly Asn Cys Tyr Phe Asp Glu 245 250 255 Asn Glu Leu Pro LysCys Lys Cys Ser Ser Gly Tyr Ser 260 265 280 amino acids amino acidlinear protein unknown 6 Arg Asp Ile Gln Ala Pro Asp Gly Leu Ala Val AspTrp Ile His Ser 1 5 10 15 Asn Ile Tyr Trp Thr Asp Ser Val Leu Gly ThrVal Ser Val Ala Asp 20 25 30 Thr Lys Gly Val Lys Arg Lys Thr Leu Phe ArgGlu Asn Gly Ser Lys 35 40 45 Pro Arg Ala Ile Val Val Asp Pro Val His GlyPhe Met Tyr Trp Thr 50 55 60 Asp Trp Gly Thr Pro Ala Lys Ile Lys Lys GlyGly Leu Asn Gly Val 65 70 75 80 Asp Ile Tyr Ser Leu Val Thr Glu Asn IleGln Trp Pro Asn Gly Ile 85 90 95 Thr Leu Asp Leu Leu Ser Gly Arg Leu TyrTrp Val Asp Ser Lys Leu 100 105 110 His Ser Ile Ser Ser Ile Asp Tyr AsnGly Gly Asn Arg Lys Thr Ile 115 120 125 Leu Glu Asp Glu Lys Arg Leu AlaHis Pro Phe Ser Leu Ala Val Phe 130 135 140 Glu Asp Lys Val Phe Trp ThrAsp Ile Ile Asn Glu Ala Ile Phe Ser 145 150 155 160 Ala Asn Arg Leu ThrGly Ser Asp Val Asn Leu Leu Ala Glu Asn Leu 165 170 175 Leu Ser Pro GluAsp Met Val Leu Phe His Asn Leu Thr Gln Pro Arg 180 185 190 Gly Val AsnTrp Cys Glu Arg Thr Thr Leu Ser Asn Gly Gly Cys Gln 195 200 205 Tyr LeuCys Leu Pro Ala Pro Gln Ile Asn Pro His Ser Pro Lys Phe 210 215 220 ThrCys Ala Cys Pro Asp Gly Met Leu Leu Ala Arg Asp Met Arg Ser 225 230 235240 Cys Leu Thr Glu Ala Glu Ala Ala Val Ala Thr Gln Glu Thr Ser Thr 245250 255 Val Arg Leu Lys Val Ser Ser Thr Ala Val Arg Thr Gln His Thr Thr260 265 270 Thr Arg Pro Val Pro Asp Thr Ser 275 280 281 amino acidsamino acid linear protein unknown 7 Thr Gly Leu Ser Asn Pro Asp Gly LeuAla Val Asp Trp Val Gly Gly 1 5 10 15 Asn Leu Tyr Trp Cys Asp Lys GlyArg Asp Thr Ile Glu Val Ser Lys 20 25 30 Leu Asn Gly Ala Tyr Arg Thr ValLeu Val Ser Ser Gly Leu Arg Glu 35 40 45 Pro Arg Ala Leu Val Val Asp ValGln Asn Gly Tyr Leu Tyr Trp Thr 50 55 60 Asp Trp Gly Asp His Ser Leu IleGly Arg Ile Gly Met Asp Gly Ser 65 70 75 80 Ser Arg Ser Val Ile Val AspThr Lys Ile Thr Trp Pro Asn Gly Leu 85 90 95 Thr Leu Asp Tyr Val Thr GluArg Ile Tyr Trp Ala Asp Ala Arg Glu 100 105 110 Asp Tyr Ile Glu Phe AlaSer Leu Asp Gly Ser Asn Arg His Val Val 115 120 125 Leu Ser Gln Asp IlePro His Ile Phe Ala Leu Thr Leu Phe Glu Asp 130 135 140 Tyr Val Tyr TrpThr Asp Trp Glu Thr Lys Ser Ile Asn Arg Ala His 145 150 155 160 Lys ThrThr Gly Thr Asn Lys Thr Leu Leu Ile Ser Thr Leu His Arg 165 170 175 ProMet Asp Leu His Val Phe His Ala Leu Arg Gln Pro Asp Val Pro 180 185 190Asn His Pro Cys Lys Val Asn Asn Gly Gly Cys Ser Asn Leu Cys Leu 195 200205 Leu Ser Pro Gly Gly Gly His Lys Cys Ala Cys Pro Thr Asn Phe Tyr 210215 220 Leu Gly Ser Asp Gly Arg Thr Cys Val Ser Asn Cys Thr Ala Ser Gln225 230 235 240 Phe Val Cys Lys Asn Asp Lys Cys Ile Pro Phe Trp Trp LysCys Asp 245 250 255 Thr Glu Asp Asp Cys Gly Asp His Ser Asp Glu Pro ProAsp Cys Pro 260 265 270 Glu Phe Lys Cys Arg Pro Gly Gln Phe 275 280 48base pairs nucleic acid single linear other nucleic acid NO NO unknownmodified_base /mod_base= i modified_base 28 /mod_base= i modified_base31 /mod_base= i modified_base 37 /mod_base= i modified_base 46/mod_base= i 8 CCARTANAGC TGRTCCTCRA AGATRTCNAG NGARTANGGR TTCATNGC 4826 base pairs nucleic acid single linear other nucleic acid NO NOunknown 9 GCGGAATTCG TNATGCARCC NGAYGG 26 26 base pairs nucleic acidsingle linear other nucleic acid NO NO unknown 10 ATAGGATCCT GRTCYTCRAADATRTC 26 2835 base pairs nucleic acid single linear cDNA NO NO unknownCDS 1..2835 11 CAA GGC TGT GAG GAG AGG ACA TGC CAT CCT GTG GGG GAT TTCCGC TGT 48 Gln Gly Cys Glu Glu Arg Thr Cys His Pro Val Gly Asp Phe ArgCys 1 5 10 15 AAA ACT CAC CAC TGC ATC CCT CTT CGT TGG CAG TGT GAT GGGCAA AAT 96 Lys Thr His His Cys Ile Pro Leu Arg Trp Gln Cys Asp Gly GlnAsn 20 25 30 GAC TGT GGA GAT AAC TCA GAT GAG GAA AAC TGT GCT CCC CGG GAGTGC 144 Asp Cys Gly Asp Asn Ser Asp Glu Glu Asn Cys Ala Pro Arg Glu Cys35 40 45 ACA GAG AGC GAG TTT CGA TGT GTC AAT CAG CAG TGC ATT CCC TCG CGA192 Thr Glu Ser Glu Phe Arg Cys Val Asn Gln Gln Cys Ile Pro Ser Arg 5055 60 TGG ATC TGT GAC CAT TAC AAC GAC TGT GGG GAC AAC TCA GAT GAA CGG240 Trp Ile Cys Asp His Tyr Asn Asp Cys Gly Asp Asn Ser Asp Glu Arg 6570 75 80 GAC TGT GAG ATG AGG ACC TGC CAT CCT GAA TAT TTT CAG TGT ACA AGT288 Asp Cys Glu Met Arg Thr Cys His Pro Glu Tyr Phe Gln Cys Thr Ser 8590 95 GGA CAT TGT GTA CAC AGT GAA CTG AAA TGC GAT GGA TCC GCT GAC TGT336 Gly His Cys Val His Ser Glu Leu Lys Cys Asp Gly Ser Ala Asp Cys 100105 110 TTG GAT GCG TCT GAT GAA GCT GAT TGT CCC ACA CGC TTT CCT GAT GGT384 Leu Asp Ala Ser Asp Glu Ala Asp Cys Pro Thr Arg Phe Pro Asp Gly 115120 125 GCA TAC TGC CAG GCT ACT ATG TTC GAA TGC AAA AAC CAT GTT TGT ATC432 Ala Tyr Cys Gln Ala Thr Met Phe Glu Cys Lys Asn His Val Cys Ile 130135 140 CCG CCA TAT TGG AAA TGT GAT GGC GAT GAT GAC TGT GGC GAT GGT TCA480 Pro Pro Tyr Trp Lys Cys Asp Gly Asp Asp Asp Cys Gly Asp Gly Ser 145150 155 160 GAT GAA GAA CTT CAC CTG TGC TTG GAT GTT CCC TGT AAT TCA CCAAAC 528 Asp Glu Glu Leu His Leu Cys Leu Asp Val Pro Cys Asn Ser Pro Asn165 170 175 CGT TTC CGG TGT GAC AAC AAT CGC TGC ATT TAT AGT CAT GAG GTGTGC 576 Arg Phe Arg Cys Asp Asn Asn Arg Cys Ile Tyr Ser His Glu Val Cys180 185 190 AAT GGT GTG GAT GAC TGT GGA GAT GGA ACT GAT GAG ACA GAG GAGCAC 624 Asn Gly Val Asp Asp Cys Gly Asp Gly Thr Asp Glu Thr Glu Glu His195 200 205 TGT AGA AAA CCG ACC CCT AAA CCT TGT ACA GAA TAT GAA TAT AAGTGT 672 Cys Arg Lys Pro Thr Pro Lys Pro Cys Thr Glu Tyr Glu Tyr Lys Cys210 215 220 GGC AAT GGG CAT TGC ATT CCA CAT GAC AAT GTG TGT GAT GAT GCCGAT 720 Gly Asn Gly His Cys Ile Pro His Asp Asn Val Cys Asp Asp Ala Asp225 230 235 240 GAC TGT GGT GAC TGG TCC GAT GAA CTG GGT TGC AAT AAA GGAAAA GAA 768 Asp Cys Gly Asp Trp Ser Asp Glu Leu Gly Cys Asn Lys Gly LysGlu 245 250 255 AGA ACA TGT GCT GAA AAT ATA TGC GAG CAA AAT TGT ACC CAATTA AAT 816 Arg Thr Cys Ala Glu Asn Ile Cys Glu Gln Asn Cys Thr Gln LeuAsn 260 265 270 GAA GGA GGA TTT ATC TGC TCC TGT ACA GCT GGG TTC GAA ACCAAT GTT 864 Glu Gly Gly Phe Ile Cys Ser Cys Thr Ala Gly Phe Glu Thr AsnVal 275 280 285 TTT GAC AGA ACC TCC TGT CTA GAT ATC AAT GAA TGT GAA CAATTT GGG 912 Phe Asp Arg Thr Ser Cys Leu Asp Ile Asn Glu Cys Glu Gln PheGly 290 295 300 ACT TGT CCC CAG CAC TGC AGA AAT ACC AAA GGA AGT TAT GAGTGT GTC 960 Thr Cys Pro Gln His Cys Arg Asn Thr Lys Gly Ser Tyr Glu CysVal 305 310 315 320 TGT GCT GAT GGC TTC ACG TCT ATG AGT GAC CGC CCT GGAAAA CGA TGT 1008 Cys Ala Asp Gly Phe Thr Ser Met Ser Asp Arg Pro Gly LysArg Cys 325 330 335 GCA GCT GAG GGT AGC TCT CCT TTG TTG CTA CTG CCT GACAAT GTC CGA 1056 Ala Ala Glu Gly Ser Ser Pro Leu Leu Leu Leu Pro Asp AsnVal Arg 340 345 350 ATT CGA AAA TAT AAT CTC TCA TCT GAG AGG TTC TCA GAGTAT CTT CAA 1104 Ile Arg Lys Tyr Asn Leu Ser Ser Glu Arg Phe Ser Glu TyrLeu Gln 355 360 365 GAT GAG GAA TAT ATC CAA GCT GTT GAT TAT GAT TGG GATCCC AAG GAC 1152 Asp Glu Glu Tyr Ile Gln Ala Val Asp Tyr Asp Trp Asp ProLys Asp 370 375 380 ATA GGC CTC AGT GTT GTG TAT TAC ACT GTG CGA GGG GAGGGC TCT AGG 1200 Ile Gly Leu Ser Val Val Tyr Tyr Thr Val Arg Gly Glu GlySer Arg 385 390 395 400 TTT GGT GCT ATC AAA CGT GCC TAC ATC CCC AAC TTTGAA TCC GGC CGC 1248 Phe Gly Ala Ile Lys Arg Ala Tyr Ile Pro Asn Phe GluSer Gly Arg 405 410 415 AAT AAT CTT GTG CAG GAA GTT GAC CTG AAA CTG AAATAC GTA ATG CAG 1296 Asn Asn Leu Val Gln Glu Val Asp Leu Lys Leu Lys TyrVal Met Gln 420 425 430 CCA GAT GGA ATA GCA GTG GAC TGG GTT GGA AGG CATATT TAC TGG TCA 1344 Pro Asp Gly Ile Ala Val Asp Trp Val Gly Arg His IleTyr Trp Ser 435 440 445 GAT GTC AAG AAT AAA CGC ATT GAG GTG GCT AAA CTTGAT GGA AGG TAC 1392 Asp Val Lys Asn Lys Arg Ile Glu Val Ala Lys Leu AspGly Arg Tyr 450 455 460 AGA AAG TGG CTG ATT TCC ACT GAC CTG GAC CAA CCAGCT GCT ATT GCT 1440 Arg Lys Trp Leu Ile Ser Thr Asp Leu Asp Gln Pro AlaAla Ile Ala 465 470 475 480 GTG AAT CCC AAA CTA GGG CTT ATG TTC TGG ACTGAC TGG GGA AAG GAA 1488 Val Asn Pro Lys Leu Gly Leu Met Phe Trp Thr AspTrp Gly Lys Glu 485 490 495 CCT AAA ATC GAG TCT GCC TGG ATG AAT GGA GAGGAC CGC AAC ATC CTG 1536 Pro Lys Ile Glu Ser Ala Trp Met Asn Gly Glu AspArg Asn Ile Leu 500 505 510 GTT TTC GAG GAC CTT GGT TGG CCA ACT GGC CTTTCT ATC GAT TAT TTG 1584 Val Phe Glu Asp Leu Gly Trp Pro Thr Gly Leu SerIle Asp Tyr Leu 515 520 525 AAC AAT GAC CGA ATC TAC TGG AGT GAC TTC AAGGAG GAC GTT ATT GAA 1632 Asn Asn Asp Arg Ile Tyr Trp Ser Asp Phe Lys GluAsp Val Ile Glu 530 535 540 ACC ATA AAA TAT GAT GGG ACT GAT AGG AGA GTCATT GCA AAG GAA GCA 1680 Thr Ile Lys Tyr Asp Gly Thr Asp Arg Arg Val IleAla Lys Glu Ala 545 550 555 560 ATG AAC CCT TAC AGC CTG GAC ATC TTT GAAGAC CAG TTA TAC TGG ATA 1728 Met Asn Pro Tyr Ser Leu Asp Ile Phe Glu AspGln Leu Tyr Trp Ile 565 570 575 TCT AAG GAA AAG GGA GAA GTA TGG AAA CAAAAT AAA TTT GGG CAA GGA 1776 Ser Lys Glu Lys Gly Glu Val Trp Lys Gln AsnLys Phe Gly Gln Gly 580 585 590 AAG AAA GAG AAA ACG CTG GTA GTG AAC CCTTGG CTC ACT CAA GTT CGA 1824 Lys Lys Glu Lys Thr Leu Val Val Asn Pro TrpLeu Thr Gln Val Arg 595 600 605 ATC TTT CAT CAA CTC AGA TAC AAT AAG TCAGTG CCC AAC CTT TGC AAA 1872 Ile Phe His Gln Leu Arg Tyr Asn Lys Ser ValPro Asn Leu Cys Lys 610 615 620 CAG ATC TGC AGC CAC CTC TGC CTT CTG AGACCT GGA GGA TAC AGC TGT 1920 Gln Ile Cys Ser His Leu Cys Leu Leu Arg ProGly Gly Tyr Ser Cys 625 630 635 640 GCC TGT CCC CAA GGC TCC AGC TTT ATAGAG GGG AGC ACC ACT GAG TGT 1968 Ala Cys Pro Gln Gly Ser Ser Phe Ile GluGly Ser Thr Thr Glu Cys 645 650 655 GAT GCA GCC ATC GAA CTG CCT ATC AACCTG CCC CCC CCA TGC AGG TGC 2016 Asp Ala Ala Ile Glu Leu Pro Ile Asn LeuPro Pro Pro Cys Arg Cys 660 665 670 ATG CAC GGA GGA AAT TGC TAT TTT GATGAG ACT GAC CTC CCC AAA TGC 2064 Met His Gly Gly Asn Cys Tyr Phe Asp GluThr Asp Leu Pro Lys Cys 675 680 685 AAG TGT CCT AGC GGC TAC ACC GGA AAATAT TGT GAA ATG GCG TTT TCA 2112 Lys Cys Pro Ser Gly Tyr Thr Gly Lys TyrCys Glu Met Ala Phe Ser 690 695 700 AAA GGC ATC TCT CCA GGA ACA ACC GCAGTA GCT GTG CTG TTG ACA ATC 2160 Lys Gly Ile Ser Pro Gly Thr Thr Ala ValAla Val Leu Leu Thr Ile 705 710 715 720 CTC TTG ATC GTC GTA ATT GGA GCTCTG GCA ATT GCA GGA TTC TTC CAC 2208 Leu Leu Ile Val Val Ile Gly Ala LeuAla Ile Ala Gly Phe Phe His 725 730 735 TAT AGA AGG ACC GGC TCC CTT TTGCCT GCT CTG CCC AAG CTG CCA AGC 2256 Tyr Arg Arg Thr Gly Ser Leu Leu ProAla Leu Pro Lys Leu Pro Ser 740 745 750 TTA AGC AGT CTC GTC AAG CCC TCTGAA AAT GGG AAT GGG GTG ACC TTC 2304 Leu Ser Ser Leu Val Lys Pro Ser GluAsn Gly Asn Gly Val Thr Phe 755 760 765 AGA TCA GGG GCA GAT CTT AAC ATGGAT ATT GGA GTG TCT GGT TTT GGA 2352 Arg Ser Gly Ala Asp Leu Asn Met AspIle Gly Val Ser Gly Phe Gly 770 775 780 CCT GAG ACT GCT ATT GAC AGG TCAATG GCA ATG AGT GAA GAC TTT GTC 2400 Pro Glu Thr Ala Ile Asp Arg Ser MetAla Met Ser Glu Asp Phe Val 785 790 795 800 ATG GAA ATG GGG AAG CAG CCCATA ATA TTT GAA AAC CCA ATG TAC TCA 2448 Met Glu Met Gly Lys Gln Pro IleIle Phe Glu Asn Pro Met Tyr Ser 805 810 815 GCC AGA GAC AGT GCT GTC AAAGTG GTT CAG CCA ATC CAG GTG ACT GTA 2496 Ala Arg Asp Ser Ala Val Lys ValVal Gln Pro Ile Gln Val Thr Val 820 825 830 TCT GAA AAT GTG GAT AAT AAGAAT TAT GGA AGT CCC ATA AAC CCT TCT 2544 Ser Glu Asn Val Asp Asn Lys AsnTyr Gly Ser Pro Ile Asn Pro Ser 835 840 845 GAG ATA GTT CCA GAG ACA AACCCA ACT TCA CCA GCT GCT GAT GGA ACT 2592 Glu Ile Val Pro Glu Thr Asn ProThr Ser Pro Ala Ala Asp Gly Thr 850 855 860 CAG GTG ACA AAA TGG AAT CTCTTC AAA CGA AAA TCT AAA CAA ACT ACC 2640 Gln Val Thr Lys Trp Asn Leu PheLys Arg Lys Ser Lys Gln Thr Thr 865 870 875 880 AAC TTT GAA AAT CCA ATCTAT GCA CAG ATG GAG AAC GAG CAA AAG GAA 2688 Asn Phe Glu Asn Pro Ile TyrAla Gln Met Glu Asn Glu Gln Lys Glu 885 890 895 AGT GTT GCT GCG ACA CCACCT CCA TCA CCT TCG CTC CCT GCT AAG CCT 2736 Ser Val Ala Ala Thr Pro ProPro Ser Pro Ser Leu Pro Ala Lys Pro 900 905 910 AAG CCT CCT TCG AGA AGAGAC CCA ACT CCA ACC TAT TCT GCA ACA GAA 2784 Lys Pro Pro Ser Arg Arg AspPro Thr Pro Thr Tyr Ser Ala Thr Glu 915 920 925 GAC ACT TTT AAA GAC ACCGCA AAT CTT GTT AAA GAA GAC TCT GAA GTA 2832 Asp Thr Phe Lys Asp Thr AlaAsn Leu Val Lys Glu Asp Ser Glu Val 930 935 940 TAG 2835 945 944 aminoacids amino acid linear protein unknown 12 Gln Gly Cys Glu Glu Arg ThrCys His Pro Val Gly Asp Phe Arg Cys 1 5 10 15 Lys Thr His His Cys IlePro Leu Arg Trp Gln Cys Asp Gly Gln Asn 20 25 30 Asp Cys Gly Asp Asn SerAsp Glu Glu Asn Cys Ala Pro Arg Glu Cys 35 40 45 Thr Glu Ser Glu Phe ArgCys Val Asn Gln Gln Cys Ile Pro Ser Arg 50 55 60 Trp Ile Cys Asp His TyrAsn Asp Cys Gly Asp Asn Ser Asp Glu Arg 65 70 75 80 Asp Cys Glu Met ArgThr Cys His Pro Glu Tyr Phe Gln Cys Thr Ser 85 90 95 Gly His Cys Val HisSer Glu Leu Lys Cys Asp Gly Ser Ala Asp Cys 100 105 110 Leu Asp Ala SerAsp Glu Ala Asp Cys Pro Thr Arg Phe Pro Asp Gly 115 120 125 Ala Tyr CysGln Ala Thr Met Phe Glu Cys Lys Asn His Val Cys Ile 130 135 140 Pro ProTyr Trp Lys Cys Asp Gly Asp Asp Asp Cys Gly Asp Gly Ser 145 150 155 160Asp Glu Glu Leu His Leu Cys Leu Asp Val Pro Cys Asn Ser Pro Asn 165 170175 Arg Phe Arg Cys Asp Asn Asn Arg Cys Ile Tyr Ser His Glu Val Cys 180185 190 Asn Gly Val Asp Asp Cys Gly Asp Gly Thr Asp Glu Thr Glu Glu His195 200 205 Cys Arg Lys Pro Thr Pro Lys Pro Cys Thr Glu Tyr Glu Tyr LysCys 210 215 220 Gly Asn Gly His Cys Ile Pro His Asp Asn Val Cys Asp AspAla Asp 225 230 235 240 Asp Cys Gly Asp Trp Ser Asp Glu Leu Gly Cys AsnLys Gly Lys Glu 245 250 255 Arg Thr Cys Ala Glu Asn Ile Cys Glu Gln AsnCys Thr Gln Leu Asn 260 265 270 Glu Gly Gly Phe Ile Cys Ser Cys Thr AlaGly Phe Glu Thr Asn Val 275 280 285 Phe Asp Arg Thr Ser Cys Leu Asp IleAsn Glu Cys Glu Gln Phe Gly 290 295 300 Thr Cys Pro Gln His Cys Arg AsnThr Lys Gly Ser Tyr Glu Cys Val 305 310 315 320 Cys Ala Asp Gly Phe ThrSer Met Ser Asp Arg Pro Gly Lys Arg Cys 325 330 335 Ala Ala Glu Gly SerSer Pro Leu Leu Leu Leu Pro Asp Asn Val Arg 340 345 350 Ile Arg Lys TyrAsn Leu Ser Ser Glu Arg Phe Ser Glu Tyr Leu Gln 355 360 365 Asp Glu GluTyr Ile Gln Ala Val Asp Tyr Asp Trp Asp Pro Lys Asp 370 375 380 Ile GlyLeu Ser Val Val Tyr Tyr Thr Val Arg Gly Glu Gly Ser Arg 385 390 395 400Phe Gly Ala Ile Lys Arg Ala Tyr Ile Pro Asn Phe Glu Ser Gly Arg 405 410415 Asn Asn Leu Val Gln Glu Val Asp Leu Lys Leu Lys Tyr Val Met Gln 420425 430 Pro Asp Gly Ile Ala Val Asp Trp Val Gly Arg His Ile Tyr Trp Ser435 440 445 Asp Val Lys Asn Lys Arg Ile Glu Val Ala Lys Leu Asp Gly ArgTyr 450 455 460 Arg Lys Trp Leu Ile Ser Thr Asp Leu Asp Gln Pro Ala AlaIle Ala 465 470 475 480 Val Asn Pro Lys Leu Gly Leu Met Phe Trp Thr AspTrp Gly Lys Glu 485 490 495 Pro Lys Ile Glu Ser Ala Trp Met Asn Gly GluAsp Arg Asn Ile Leu 500 505 510 Val Phe Glu Asp Leu Gly Trp Pro Thr GlyLeu Ser Ile Asp Tyr Leu 515 520 525 Asn Asn Asp Arg Ile Tyr Trp Ser AspPhe Lys Glu Asp Val Ile Glu 530 535 540 Thr Ile Lys Tyr Asp Gly Thr AspArg Arg Val Ile Ala Lys Glu Ala 545 550 555 560 Met Asn Pro Tyr Ser LeuAsp Ile Phe Glu Asp Gln Leu Tyr Trp Ile 565 570 575 Ser Lys Glu Lys GlyGlu Val Trp Lys Gln Asn Lys Phe Gly Gln Gly 580 585 590 Lys Lys Glu LysThr Leu Val Val Asn Pro Trp Leu Thr Gln Val Arg 595 600 605 Ile Phe HisGln Leu Arg Tyr Asn Lys Ser Val Pro Asn Leu Cys Lys 610 615 620 Gln IleCys Ser His Leu Cys Leu Leu Arg Pro Gly Gly Tyr Ser Cys 625 630 635 640Ala Cys Pro Gln Gly Ser Ser Phe Ile Glu Gly Ser Thr Thr Glu Cys 645 650655 Asp Ala Ala Ile Glu Leu Pro Ile Asn Leu Pro Pro Pro Cys Arg Cys 660665 670 Met His Gly Gly Asn Cys Tyr Phe Asp Glu Thr Asp Leu Pro Lys Cys675 680 685 Lys Cys Pro Ser Gly Tyr Thr Gly Lys Tyr Cys Glu Met Ala PheSer 690 695 700 Lys Gly Ile Ser Pro Gly Thr Thr Ala Val Ala Val Leu LeuThr Ile 705 710 715 720 Leu Leu Ile Val Val Ile Gly Ala Leu Ala Ile AlaGly Phe Phe His 725 730 735 Tyr Arg Arg Thr Gly Ser Leu Leu Pro Ala LeuPro Lys Leu Pro Ser 740 745 750 Leu Ser Ser Leu Val Lys Pro Ser Glu AsnGly Asn Gly Val Thr Phe 755 760 765 Arg Ser Gly Ala Asp Leu Asn Met AspIle Gly Val Ser Gly Phe Gly 770 775 780 Pro Glu Thr Ala Ile Asp Arg SerMet Ala Met Ser Glu Asp Phe Val 785 790 795 800 Met Glu Met Gly Lys GlnPro Ile Ile Phe Glu Asn Pro Met Tyr Ser 805 810 815 Ala Arg Asp Ser AlaVal Lys Val Val Gln Pro Ile Gln Val Thr Val 820 825 830 Ser Glu Asn ValAsp Asn Lys Asn Tyr Gly Ser Pro Ile Asn Pro Ser 835 840 845 Glu Ile ValPro Glu Thr Asn Pro Thr Ser Pro Ala Ala Asp Gly Thr 850 855 860 Gln ValThr Lys Trp Asn Leu Phe Lys Arg Lys Ser Lys Gln Thr Thr 865 870 875 880Asn Phe Glu Asn Pro Ile Tyr Ala Gln Met Glu Asn Glu Gln Lys Glu 885 890895 Ser Val Ala Ala Thr Pro Pro Pro Ser Pro Ser Leu Pro Ala Lys Pro 900905 910 Lys Pro Pro Ser Arg Arg Asp Pro Thr Pro Thr Tyr Ser Ala Thr Glu915 920 925 Asp Thr Phe Lys Asp Thr Ala Asn Leu Val Lys Glu Asp Ser GluVal 930 935 940 945 207 amino acids amino acid linear peptide NOC-terminal unknown 13 Arg Arg Thr Gly Ser Leu Leu Pro Ala Leu Pro LysLeu Pro Ser Leu 1 5 10 15 Ser Ser Leu Val Lys Pro Ser Glu Asn Gly AsnGly Val Thr Phe Arg 20 25 30 Ser Gly Ala Asp Leu Asn Met Asp Ile Gly ValSer Gly Phe Gly Pro 35 40 45 Glu Thr Ala Ile Asp Arg Ser Met Ala Met SerGlu Asp Phe Val Met 50 55 60 Glu Met Gly Lys Gln Pro Ile Ile Phe Glu AsnPro Met Tyr Ser Ala 65 70 75 80 Arg Asp Ser Ala Val Lys Val Val Gln ProIle Gln Val Thr Val Ser 85 90 95 Glu Asn Val Asp Asn Lys Asn Tyr Gly SerPro Ile Asn Pro Ser Glu 100 105 110 Ile Val Pro Glu Thr Asn Pro Thr SerPro Ala Ala Asp Gly Thr Gln 115 120 125 Val Thr Lys Trp Asn Leu Phe LysArg Lys Ser Lys Gln Thr Thr Asn 130 135 140 Phe Glu Asn Pro Ile Tyr AlaGln Met Glu Asn Glu Gln Lys Glu Ser 145 150 155 160 Val Ala Ala Thr ProPro Pro Ser Pro Ser Leu Pro Ala Lys Pro Lys 165 170 175 Pro Pro Ser ArgArg Asp Pro Thr Pro Thr Tyr Ser Ala Thr Glu Asp 180 185 190 Thr Phe LysAsp Thr Ala Asn Leu Val Lys Glu Asp Ser Glu Val 195 200 205 7 aminoacids amino acid linear peptide NO internal unknown 14 Pro Ser Leu ProAla Lys Pro 1 5 7 amino acids amino acid linear peptide NO internalunknown 15 Ser Leu Leu Pro Ala Leu Pro 1 5 7 amino acids amino acidlinear peptide NO internal unknown 16 Pro Ala Leu Pro Lys Leu Pro 1 56412 base pairs nucleic acid single linear cDNA NO NO unknown 17GAATTCTGTC AATGAGCTGG CCTTCCTTAT AAAAGGATTT ACATTTTCTG CTTAAGAGGT 60ATTATTTATA GTTTGAAATA TTTCTGGTGA TATTTGCGGG TGGGATCATA TGTGCTTCAT 120TGTGCATTTT ATAAAGAACA ACAAATTCAC GGGAAGATGT GCCTTTTGAT GTTGTTGCTT 180TGCAAATTTT GCTGAGAAGA GTCGTTGATA TTTCCTGTTG TTTAGAAGGA ATCGGCACAT 240TTATTAGAAA TTGGTGATTG CTCTTCTTGA TGGAAAAGTG ACTCAGAATA TAGTTAAAAG 300GTTAATGGGC AGAACTTCCA TGGCGCTTCT TAGGGAGCAT TTAATGTAGA AGCTGTTGCA 360AGTGCTATTG TGGAGGGGTC AATGTGAACG GTGGCTGCAT CCATCTTTTA CTTCTTCTGG 420GATTATCTTT CTTCAGGTCC GGGTGGTGCC GAGTGCCAGT GTCCACATGA GGGCAACTGG 480TATTTGGCCA ACAACAGGAA GCACTGCATT GTGGACAATG GTGAACGATG TGGTGCATCT 540TCCTTCACCT GCTCCAATGG GCGCTGCATC TCGGAAGAGT GGAAGTGTGA TAATGACAAC 600GACTGTGGGG ATGGCAGTGA TGAGATGGAA AGTGTCTGTG CACTTCACAC CTGCTCACCG 660ACAGCCTTCA CCTGTGCCAA TGGGCGATGT GTCCAATACT CTTACCGCTG TGATTACTAC 720AATGACTGTG GTGATGGCAG TGATGAGGCA GGGTGCCTGT TCAGGGACTG CAATGCCACC 780ACGGAGTTTA TGTGCAATAA CAGAAGGTGC ATACCTCGTG AGTTTATCTG CAATGGTGTA 840GACAACTGCC ATGATAATAA CACTTCAGAT GAGAAAAATT GCCCTGATCG CACTTGCCAG 900TCTGGATACA CAAAATGTCA TAATTCAAAT ATTTGTATTC CTCGCGTTTA TTTGTGTGAC 960GGAGACAATG ACTGTGGAGA TAACAGTGAT GAAAACCCTA CTTATTGCAC CACTCACACA 1020TGCAGCAGTG AGTTCCAATG CACATCTGGG NGCTGTATTC CTCAACATTG GTATTGTGAT 1080CAAGAAACAG ATTGTTTTGA TGCCTCTCGA TGAACCTGCC TCCTTGTGGT CACTCTGAGC 1140GAACATGCCT AGCTGATGAG TTCAAGTGTG ATGGTGGGAG GTGCATCCCA AGCGAATGGA 1200TCTGTGACGG TGATAATGAC TGTGGGGATA TGAGTGACGA GGATAAAAGG CACCAGTGTC 1260AGAATCAAAA CTGCTCGGAT TCCGAGTTTC TCTGTGTAAA TGACAGACCT CCGGACAGGA 1320GTGCATTCCC CAGTCTTGGG TCTGTGATGG CGATGTGGAT TGTACTGACG GCTACATGAG 1380AATCAGAATT GCACCAGGAG AACTTGCTCT GAAAATGAAT TCACCTGTGG TTACGGAATG 1440TGTATCCCAA AGATATTGCG AGGTGTGACC GGCACAATGA CTGTGGTGAC TATAGCGACG 1500AGAGGGCTGC TTATACCTAG ACTTGCCAAC AGAATCAGTT TCCTGTCAGA ACGGGCGCTG 1560CATTAGTAAA ACCTTCGTCT GTGATGCAGG ATGAATCGAC TGTGGAGACG GATCTGATGA 1620GCTGATGCAC CTGTGCCACA CCCCACGTGT CCACCTCACG AGTGTCAAAT ATGACAATGG 1680GCGCTGCATC GAGATGATGA AACTCTGCAA CCACCTAGAT GACTGTTTGG ACAACAGCGA 1740TGAGAAAGGC TGTGGCATTA ATGAATGCCA TGACCCTTCA ATCAGTGGCT GCGATCACAA 1800CTGTATAGAC ACCTTAACCA GTTTCTATTG TTCCTGTCGT CCTGGTTACA AGCTCATGTC 1860TGACAAGCGG ACTTGTGTTG ATATTGATGA ATGCACAGAG ATGCCTTTTG TCTGTAGCCA 1920GAAGTGTGAG AATGTAATAG GCTCCTACAT CTGTAAGTGT GCCCCAGGCT ACCTCCGAGA 1980ACCAGATGGA AAGACCTGCC GGCAAAACAG TAACATCGAA CCCTATCTCA TTTTTAGCAA 2040CCGTTACTAT TTGAGAAATT TAACTATAGA TGGCTATTTT TACTCCCTCA TCTTGGAAGG 2100ACTGGACAAT GTTGTGGCAT TAGATTTTGA CCGAGTAGAG AAGAGATTGT ATTGGATTGA 2160TACACAGAGG CAAGTCATTG AGAGAATGTT TCTGAATAAG ACAAACAAGG AGACAATCAT 2220AAACCACAGA CTACCAGCTG CAGAAAGTCT GGCTGTAGAC TGGGTTTCCA GAAAGCTCTA 2280CTGGTTGGAT GCCCGCCTGG ATGGCCTCTT TGTCTCTGAC CTCAATGGTG GACACCGCCG 2340CATGCTGGCC CAGCACTGTG TGGATGCCAA CAACACCTTC TGCTTTGATA ATCCCAGAGG 2400ACTTGCCCTT CACCCTCAAT ATGGGTACCT CTACTGGGCA GACTGGGGTC ACCGCGCATA 2460CATTGGGAGA GTAGGCATGG ATGGAACCAA CAAGTCTGTG ATACTCCACC AAGTTAGAGT 2520TGGCCTAATG GCATCACCAT TGATTACACC AATGATCTAC TCTACTGGGC AGATGCCACC 2580CTGGGTTACA TAGAGTACTC TGATTTGGAG GGCCACCATC GACACACGGT GTATGATGGG 2640GCACTGCCTC ACCCTTTCGC TATTACCATT TTTGAAGACA CTATTTATTG GACAGATTGG 2700AATACAAGGA CAGTGGAAAA GGGAAACAAA TATGATGGAT CAAATAGACA GACACTGGTG 2760AACACAACAC ACAGACCATT TGACATCCAT GTGTACCATC CATATAGGCA GCCCGTACCA 2820TCCATATAGG CAGCCCATTG TGAGCAATCC CTGTGGTACC AACAATGGTG GCTGTTCTCA 2880TCTCTGCCTC ATCAAGCCAG GAGGAAAAGG GTTCACTTGC GAGTGTCCAG ATGACTTCCG 2940CACCCTTCAA CTGAGTGGCA GCACCTACTG CATGCCCATG TGCTCCAGCA CCCAGTTCCT 3000GTGCGCTAAC AATGAAAAGT GCATTCCTAT CTGGTGGAAA TGTGATGGAC AGAAAGACTG 3060CTCAGATGGC TCTGATGAAC TGGCCCTTTG CCCGCAGCGC TTCTGCCGAC TGGGACAGTT 3120CCAGTGCAGT GACGGCAACT GCACCAGCCC GCAGACTTTA TGCAATGCTC ACCAAAATTG 3180CCCTCGATGG TCTGATGAAG ACCGTCTTCT TTGTGAGAAT CACCACTGTG ACTCCAATGA 3240ATGGCAGTGC GCCAACAAAC GTTGCATCCC AGAATCCTGG CAGTGTGACA CATTTAACGA 3300CTGTGAGGAT AACTCAGATG AAGACAGTTC CCACTGTGCC AGCAGGACCT GCCGGCCGGG 3360CCAGTTTCGG TGTGCTAATG GCCGCTGCAT CCCGCAGGCC TGGAAGTGTG ATGTGGATAA 3420TGATTGTGGA GACCACTCGG ATGAGCCCAT TGAAGAATGC ATGAGCTCTG CCCATCTCTG 3480TGACAACTTC ACAGAATTCA GCTGCAAAAC AAATTACCGC TGCATCCCAA AGTGGGCCGT 3540GTGCAATGGT GTAGATGACT GCAGGGACAA CAGTGATGAG CAAGGCTGTG AGGAGAGGAC 3600ATGCCATCCT GTGGGGGATT TCCGCTGTAA AACTCACCAC TGCATCCCTC TTCGTTGGCA 3660GTGTGATGGG CAAAATGACT GTGGAGATAA CTCAGATGAG GAAAACTGTG CTCCCCGGGA 3720GTGCACAGAG AGCGAGTTTC GATGTGTCAA TCAGCAGTGC ATTCCCTCGC GATGGATCTG 3780TGACCATTAC AACGACTGTG GGGACAACTC AGATGAACGG GACTGTGAGA TGAGGACCTG 3840CCATCCTGAA TATTTTCAGT GTACAAGTGG ACATTGTGTA CACAGTGAAC TGAAATGCGA 3900TGGATCCGCT GACTGTTTGG ATGCGTCTGA TGAAGCTGAT TGTCCCACAC GCTTTCCTGA 3960TGGTGCATAC TGCCAGGCTA CTATGTTCGA ATGCAAAAAC CATGTTTGTA TCCCGCCATA 4020TTGGAAATGT GATGGCGATG ATGACTGTGG CGATGGTTCA GATGAAGAAC TTCACCTGTG 4080CTTGGATGTT CCCTGTAATT CACCAAACCG TTTCCGGTGT GACAACAATC GCTGCATTTA 4140TAGTCATGAG GTGTGCAATG GTGTGGATGA CTGTGGAGAT GGAACTGATG AGACAGAGGA 4200GCACTGTAGA AAACCGACCC CTAAACCTTG TACAGAATAT GAATATAAGT GTGGCAATGG 4260GCATTGCATT CCACATGACA ATGTGTGTGA TGATGCCGAT GACTGTGGTG ACTGGTCCGA 4320TGAACTGGGT TGCAATAAAG GAAAAGAAAG AACATGTGCT GAAAATATAT GCGAGCAAAA 4380TTGTACCCAA TTAAATGAGG AGGATTTATC TGCTCCTGTA CAGCTGGGTT CGAAACCAAT 4440GTTTTTTGAC AGAACCTCCT GTCTAGATAT CAATGAATGT GAACAATTTG GGACTTGTCC 4500CCAGCACTGC AGAAATACCA AAGGAAGTTA TGAGTGTGTC TGTGCTGATG GCTTCACGTC 4560TATGAGTGAC CGCCCTGGAA AACGATGTGC AGCTGAGGGT AGCTCTCCTT TGTTGCTACT 4620GCCTGACAAT GTCCGAATTC GAAAATATAA TCTCTCATCT GAGAGGTTCT CAGAGTATCT 4680TCAAGATGAG GAATATATCC AAGCTGTTGA TTATGATTGG GATCCCAAGG ACATAGGCCT 4740CAGTGTTGTG TATTACACTG TGCGAGGGGA GGGCTCTAGG TTTGGTGCTA TCAAACGTGC 4800CTACATCCCC AACTTTGAAT CCGGCCGCAA TAATCTTGTG CAGGAAGTTG ACCTGAAACT 4860GAAATACGTA ATGCAGCCAG ATGGAATAGC AGTGGACTGG GTTGGAAGGC ATATTTACTG 4920GTCAGATGTC AAGAATAAAC GCATTGAGGT GGCTAAACTT GATGGAAGGT ACAGAAAGTG 4980GCTGATTTCC ACTGACCTGG ACCAACCAGC TGCTATTGCT GTGAATCCCA AACTAGGGCT 5040TATGTTCTGG ACTGACTGGG GAAAGGAACC TAAAATCGAG TCTGCCTGGA TGAATGGAGA 5100GGACCGCAAC ATCCTGGTTT TCGAGGACCT TGGTTGGCCA ACTGGCCTTT CTATCGATTA 5160TTTGAACGAC CGAATCTACT GGAGTGACTT CAAGGAGGAC GTTATTGAAA CCATAAAATA 5220TGATGGGACT GATAGGAGAG TCATTGCAAA GGAAGCAATG AACCCTTACA GCCTGGACAT 5280CTTTGAAGAC CAGTTATACT GGATATCTAA GGAAAAGGGA GAAGTATGGA AACAAAATAA 5340ATTTGGGCAA GGAAAGAAAG AGAAAACGCT GGTAGTGAAC CCTTGGCTCA CTCAAGTTCG 5400AATCTTTCAT CAACTCAGAT ACAATAAGTC AGTGCCCAAC CTTTGCAAAC AGATCTGCAG 5460CCACCTCTGC CTTCTGAGAC CTGGAGGATA CAGCTGTGCC TGTCCCCAAG GCTCCAGCTT 5520TATAGAGGGG AGCACCACTG AGTGTGATGC AGCCATCGAA CTGCCTATCA ACCTGCCCCC 5580CCCATGCAGG TGCATGCACG GAGGAAATTG CTATTTTGAT GAGACTGACC TCCCCAAATG 5640CAAGTGTCCT AGCGGCTACA CCGGAAAATA TTGTGAAATG GCGTTTTCAA AAGGCATCTC 5700TCCAGGAACA ACCGCAGTAG CTGTGCTGTT GACAATCCTC TTGATCGTCG TAATTGGAGC 5760TCTGGCAATT GCAGGATTCT TCCACTATAG AAGGACCGGC TCCCTTTTGC CTGCTCTGCC 5820CAAGCTGCCA AGCTTAAGCA GTCTCGTCAA GCCCTCTGAA AATGGGAATG GGGTGACCTT 5880CAGATCAGGG GCAGATCTTA ACATGGATAT TGGAGTGTCT GGTTTTGGAC CTGAGACTGC 5940TATTGACAGG TCAATGGCAA TGAGTGAAGA CTTTGTCATG GAAATGGGGA AGCAGCCCAT 6000AATATTTGAA AACCCAATGT ACTCAGCCAG AGACAGTGCT GTCAAAGTGG TTCAGCCAAT 6060CCAGGTGACT GTATCTGAAA ATGTGGATAA TAAGAATTAT GGAAGTCCCA TAAACCCTTC 6120TGAGATAGTT CCAGAGACAA ACCCAACTTC ACCAGCTGCT GATGGAACTC AGGTGACAAA 6180ATGGAATCTC TTCAAACGAA AATCTAAACA AACTACCAAC TTTGAAAATC CAATCTATGC 6240ACAGATGGAG AACGAGCAAA AGGAAAGTGT TGCTGCGACA CCACCTCCAT CACCTTCGCT 6300CCCTGCTAAG CCTAAGCCTC CTTCGAGAAG AGACCCAACT CCAACCTATT CTGCAACAGA 6360AGACACTTTT AAAGACACCG CAAATCTTGT TAAAGAAGAC TCTGAAGTAT AG 6412 19 aminoacids amino acid linear peptide NO internal unknown 18 Ala Thr Pro ProPro Ser Pro Ser Leu Pro Ala Lys Pro Lys Pro Pro 1 5 10 15 Ser Arg Arg 12amino acids amino acid linear peptide NO internal unknown 19 Phe Glu AsnPro Ile Tyr Ala Gln Met Glu Asn Glu 1 5 10 9 amino acids amino acidlinear peptide NO internal unknown 20 Arg Xaa Leu Pro Pro Arg Pro XaaXaa 1 5 9 amino acids amino acid linear peptide NO internal unknownModified-site /label= hydrophobic 21 Arg Xaa Leu Pro Pro Leu Pro Arg Xaa1 5 11 amino acids amino acid linear peptide NO internal unknown 22 ProThr Met Pro Pro Pro Leu Pro Pro Val Pro 1 5 10 11 amino acids amino acidlinear peptide NO internal unknown 23 Pro Ala Tyr Pro Pro Pro Pro ValPro Val Pro 1 5 10 11 amino acids amino acid linear peptide NO internalunknown 24 Glu Val Pro Val Pro Pro Pro Val Pro Pro Arg 1 5 10 11 aminoacids amino acid linear peptide NO internal unknown 25 His Leu Asp SerPro Pro Ala Ile Pro Pro Arg 1 5 10 11 amino acids amino acid linearpeptide NO internal unknown 26 His Ser Ile Ala Gly Pro Pro Val Pro ProArg 1 5 10 11 amino acids amino acid linear peptide NO internal unknown27 Ala Pro Ala Val Pro Pro Ala Arg Pro Gly Ser 1 5 10 11 amino acidsamino acid linear peptide NO internal unknown 28 Gly Ala Pro Pro Val ProSer Arg Pro Gly Ala 1 5 10 11 amino acids amino acid linear peptide NOinternal unknown 29 Pro Pro Arg Pro Leu Pro Val Ala Pro Gly Ser 1 5 1011 amino acids amino acid linear peptide NO internal unknown 30 Pro AlaPro Ala Leu Pro Pro Lys Pro Pro Lys 1 5 10 11 amino acids amino acidlinear peptide NO internal unknown 31 Ala Pro Lys Pro Met Pro Pro ArgPro Pro Leu 1 5 10 11 amino acids amino acid linear peptide NO internalunknown 32 Pro Pro Thr Pro Pro Pro Leu Pro Pro Pro Leu 1 5 10 11 aminoacids amino acid linear peptide NO internal unknown 33 Pro Ala Leu ProPro Pro Pro Arg Pro Val Pro 1 5 10 11 amino acids amino acid linearpeptide NO internal unknown 34 Arg Pro Arg Pro Leu Pro Pro Leu Pro ProThr 1 5 10 11 amino acids amino acid linear peptide NO internal unknown35 Gly Val Arg Pro Leu Pro Pro Leu Pro Asp Pro 1 5 10 11 amino acidsamino acid linear peptide NO internal unknown 36 Pro Pro Arg Pro Leu ProPro Arg Pro Pro Ala 1 5 10 7 amino acids amino acid linear peptide NOinternal unknown Modified-site /label= hydrophobic 37 Xaa Pro Xaa ProPro Xaa Pro 1 5 22 amino acids amino acid linear peptide NO internalunknown 38 Glu Ser Asp Gly Gly Tyr Met Asp Met Ser Lys Asp Glu Ser ValAsp 1 5 10 15 Tyr Val Pro Met Leu Asp 20 18 amino acids amino acidlinear peptide NO internal unknown 39 Glu Glu Glu Glu Glu Tyr Met ProMet Glu Asp Leu Tyr Leu Asp Ile 1 5 10 15 Leu Pro 11 amino acids aminoacid linear peptide NO internal unknown 40 Gln Gly Val Asp Thr Tyr ValGlu Met Arg Pro 1 5 10 11 amino acids amino acid linear peptide NOinternal unknown 41 Asp Ser Thr Asn Glu Tyr Met Asp Met Lys Pro 1 5 1024 amino acids amino acid linear peptide NO internal unknown 42 Gly ProGly Gly Asp Tyr Ala Ala Met Gly Ala Cys Pro Ala Ser Glu 1 5 10 15 GlnGly Tyr Glu Glu Met Arg Ala 20 27 amino acids amino acid linear peptideNO internal unknown 43 Thr Pro Asp Glu Asp Tyr Glu Tyr Met Asn Arg GlnArg Asp Gly Gly 1 5 10 15 Gly Pro Gly Gly Asp Tyr Ala Ala Met Gly Ala 2025 11 amino acids amino acid linear peptide NO internal unknown 44 CysThr Ile Asp Val Tyr Met Val Met Val Lys 1 5 10 11 amino acids amino acidlinear peptide NO internal unknown 45 Ser Pro Ser Ser Gly Tyr Met ProMet Asn Gln 1 5 10 11 amino acids amino acid linear peptide NO internalunknown 46 Asp Glu Asp Glu Glu Tyr Glu Tyr Met Asn Arg 1 5 10 11 aminoacids amino acid linear peptide NO internal unknown 47 Leu Glu Glu LeuGly Tyr Glu Tyr Met Asp Val 1 5 10 11 amino acids amino acid linearpeptide NO internal unknown 48 Glu Glu Leu Ser Asn Tyr Ile Cys Met GlyGly 1 5 10 11 amino acids amino acid linear peptide NO internal unknown49 Val Ser Ile Glu Glu Tyr Thr Glu Met Met Pro 1 5 10 11 amino acidsamino acid linear peptide NO internal unknown 50 His Thr Asp Asp Gly TyrMet Pro Met Ser Pro 1 5 10 11 amino acids amino acid linear peptide NOinternal unknown 51 Lys Gly Asn Gly Asp Tyr Met Pro Met Ser Pro 1 5 1011 amino acids amino acid linear peptide NO internal unknown 52 Val AspPro Asn Gly Tyr Met Met Met Ser Pro 1 5 10 11 amino acids amino acidlinear peptide NO internal unknown 53 Pro Cys Thr Gly Asp Tyr Met AsnMet Ser Pro 1 5 10 11 amino acids amino acid linear peptide NO internalunknown 54 Thr Gly Ser Glu Glu Tyr Met Asn Met Asp Leu 1 5 10 11 aminoacids amino acid linear peptide NO internal unknown 55 Asn Ser Arg GlyAsp Tyr Met Thr Met Gln Ile 1 5 10 11 amino acids amino acid linearpeptide NO internal unknown 56 Val Ala Pro Val Ser Tyr Ala Asp Met ArgThr 1 5 10 21 amino acids amino acid linear peptide NO internal unknown57 Glu Arg Glu Asn Glu Tyr Met Pro Met Ala Pro Gln Ile His Leu Tyr 1 510 15 Ser Gln Ile Arg Glu 20 11 amino acids amino acid linear peptide NOinternal unknown 58 Leu Ser Asn Pro Thr Tyr Ser Val Met Arg Ser 1 5 1011 amino acids amino acid linear peptide NO internal unknown 59 Cys ProGlu Lys Val Tyr Glu Leu Met Arg Ala 1 5 10 21 amino acids amino acidlinear peptide NO internal unknown 60 Asn Thr Thr Val Asp Tyr Val TyrMet Ser His Gly Asp Asn Gly Asp 1 5 10 15 Tyr Val Tyr Met Asn 20 21amino acids amino acid linear peptide NO internal unknown 61 Asn Cys AsnAsp Asp Tyr Val Thr Met His Tyr Thr Thr Asp Gly Asp 1 5 10 15 Tyr IleTyr Met Asn 20 27 amino acids amino acid linear peptide NO internalunknown 62 Tyr Val Asn Asp Ile Tyr Leu Tyr Met Arg His Leu Glu Arg GluPhe 1 5 10 15 Lys Val Arg Thr Asp Tyr Met Ala Met Gln Glu 20 25 11 aminoacids amino acid linear peptide NO internal unknown 63 Asn Gln Glu GluAla Tyr Val Thr Met Ser Ser 1 5 10 11 amino acids amino acid linearpeptide NO internal unknown 64 Phe Ile Ala Ser Lys Tyr Glu Asp Met TyrPro 1 5 10 11 amino acids amino acid linear peptide NO internal unknown65 Leu Gly Ser Gln Ser Tyr Glu Asp Met Arg Gly 1 5 10 11 amino acidsamino acid linear peptide NO internal unknown 66 Glu Asp Ala Asp Ser TyrGlu Asn Met Asp Lys 1 5 10 11 amino acids amino acid linear peptide NOinternal unknown 67 Glu Leu Gln Asp Asp Tyr Glu Asp Met Met Glu 1 5 1011 amino acids amino acid linear peptide NO internal unknown 68 Ala AlaCys Val Val Tyr Glu Asp Met Ser His 1 5 10 11 amino acids amino acidlinear peptide NO internal unknown 69 Ala Pro Pro Glu Glu Tyr Val ProMet Val Lys 1 5 10 11 amino acids amino acid linear peptide NO internalunknown 70 Ile Asp Ser Cys Thr Tyr Glu Ala Met Tyr Asn 1 5 10 11 aminoacids amino acid linear peptide NO internal unknown 71 Val Ala Val AlaGlu Tyr Glu Ile Met Glu Gln 1 5 10 11 amino acids amino acid linearpeptide NO internal unknown 72 Met Ser Val Glu Ser Tyr Glu Glu Met LysMet 1 5 10 11 amino acids amino acid linear peptide NO internal unknown73 His Gln Thr Arg Glu Tyr Glu Ser Met Ile Glu 1 5 10 11 amino acidsamino acid linear peptide NO internal unknown 74 Thr Leu Gln Asn Glu TyrGlu Leu Met Arg Glu 1 5 10 11 amino acids amino acid linear peptide NOinternal unknown 75 Gly Gly Glu Glu Ile Tyr Val Val Met Leu Gly 1 5 1011 amino acids amino acid linear peptide NO internal unknown 76 Leu GluGly Glu His Tyr Ile Asn Met Ala Val 1 5 10 11 amino acids amino acidlinear peptide NO internal unknown 77 Glu Ile Thr Glu Gln Tyr Ile TyrMet Val Met 1 5 10 11 amino acids amino acid linear peptide NO internalunknown 78 Thr Glu Gln Tyr Ile Tyr Met Val Met Glu Cys 1 5 10 5 aminoacids amino acid linear peptide NO internal unknown 79 Leu Pro Ala LysPro 1 5 5 amino acids amino acid linear peptide NO internal unknown 80Leu Pro Ala Leu Pro 1 5 5 amino acids amino acid linear peptide NOinternal unknown 81 Leu Pro Lys Leu Pro 1 5 11 amino acids amino acidlinear peptide NO internal unknown 82 Glu Asn Pro Ile Tyr Ala Gln MetGlu Asn Glu 1 5 10 14086 base pairs nucleic acid single linear cDNA NONO Homo sapiens CDS 107..14074 83 TTGCAGACCT AAAGGAGCGT TCGCTAGCAGAGGCGCTGCC GGTGCGGTGT GCTACGCGCG 60 CCCACCTCCC GGGGAAGGAA CGGCGAGGCCGGGGACCGTC GCGGAG ATG GAT CGC 115 Met Asp Arg GGG CCG GCA GCA GTG GCGTGC ACG CTG CTC CTG GCT CTC GTC GCC TGC 163 Gly Pro Ala Ala Val Ala CysThr Leu Leu Leu Ala Leu Val Ala Cys 950 955 960 CTA GCG CCG GCC AGT GGCCAA GAA TGT GAC AGT GCG CAT TTT CGC TGT 211 Leu Ala Pro Ala Ser Gly GlnGlu Cys Asp Ser Ala His Phe Arg Cys 965 970 975 980 GGA AGT GGG CAT TGCATC CCT GCA GAC TGG AGG TGT GAT GGG ACC AAA 259 Gly Ser Gly His Cys IlePro Ala Asp Trp Arg Cys Asp Gly Thr Lys 985 990 995 GAC TGT TCA GAT GACGCG GAT GAA ATT GGC TGC GCT GTT GTG ACC TGC 307 Asp Cys Ser Asp Asp AlaAsp Glu Ile Gly Cys Ala Val Val Thr Cys 1000 1005 1010 CAG CAG GGC TATTTC AAG TGC CAG AGT GAG GGA CAA TGC ATC CCC AGC 355 Gln Gln Gly Tyr PheLys Cys Gln Ser Glu Gly Gln Cys Ile Pro Ser 1015 1020 1025 TCC TGG GTGTGT GAC CAA GAT CAA GAC TGT GAT GAT GGC TCA GAT GAA 403 Ser Trp Val CysAsp Gln Asp Gln Asp Cys Asp Asp Gly Ser Asp Glu 1030 1035 1040 CGT CAAGAT TGC TCA CAA AGT ACA TGC TCA AGT CAT CAG ATA ACA TGC 451 Arg Gln AspCys Ser Gln Ser Thr Cys Ser Ser His Gln Ile Thr Cys 1045 1050 1055 1060TCC AAT GGT CAG TGT ATC CCA AGT GAA TAC AGG TGC GAC CAC GTC AGA 499 SerAsn Gly Gln Cys Ile Pro Ser Glu Tyr Arg Cys Asp His Val Arg 1065 10701075 GAC TGC CCC GAT GGA GCT GAT GAG AAT GAC TGC CAG TAC CCA ACA TGT 547Asp Cys Pro Asp Gly Ala Asp Glu Asn Asp Cys Gln Tyr Pro Thr Cys 10801085 1090 GAG CAG CTT ACT TGT GAC AAT GGG GCC TGC TAT AAC ACC AGT CAGAAG 595 Glu Gln Leu Thr Cys Asp Asn Gly Ala Cys Tyr Asn Thr Ser Gln Lys1095 1100 1105 TGT GAT TGG AAA GTT GAT TGC AGG GAC TCC TCA GAT GAA ATCAAC TGC 643 Cys Asp Trp Lys Val Asp Cys Arg Asp Ser Ser Asp Glu Ile AsnCys 1110 1115 1120 ACT GAG ATA TGC TTG CAC AAT GAG TTT TCA TGT GGC AATGGA GAG TGT 691 Thr Glu Ile Cys Leu His Asn Glu Phe Ser Cys Gly Asn GlyGlu Cys 1125 1130 1135 1140 ATC CCT CGT GCT TAT GTC TGT GAC CAT GAC AATGAT TGC CAA GAC GGC 739 Ile Pro Arg Ala Tyr Val Cys Asp His Asp Asn AspCys Gln Asp Gly 1145 1150 1155 AGT GAT GAA CAT GCT TGC AAC TAT CCG ACCTGC GGT GGT TAC CAG TTC 787 Ser Asp Glu His Ala Cys Asn Tyr Pro Thr CysGly Gly Tyr Gln Phe 1160 1165 1170 ACT TGC CCC AGT GGC CGA TGC ATT TATCAA AAC TGG GTT TGT GAT GGA 835 Thr Cys Pro Ser Gly Arg Cys Ile Tyr GlnAsn Trp Val Cys Asp Gly 1175 1180 1185 GAA GAT GAC TGT AAA GAT AAT GGAGAT GAA GAT GGA TGT GAA AGC GGT 883 Glu Asp Asp Cys Lys Asp Asn Gly AspGlu Asp Gly Cys Glu Ser Gly 1190 1195 1200 CCT CAT GAT GTT CAT AAA TGTTCC CCA AGA GAA TGG TCT TGC CCA GAG 931 Pro His Asp Val His Lys Cys SerPro Arg Glu Trp Ser Cys Pro Glu 1205 1210 1215 1220 TCG GGA CGA TGC ATCTCC ATT TAT AAA GTT TGT GAT GGG ATT TTA GAT 979 Ser Gly Arg Cys Ile SerIle Tyr Lys Val Cys Asp Gly Ile Leu Asp 1225 1230 1235 TGC CCA GGA AGAGAA GAT GAA AAC AAC ACT AGT ACC GGA AAA TAC TGT 1027 Cys Pro Gly Arg GluAsp Glu Asn Asn Thr Ser Thr Gly Lys Tyr Cys 1240 1245 1250 AGT ATG ACTCTG TGC TCT GCC TTG AAC TGC CAG TAC CAG TGC CAT GAG 1075 Ser Met Thr LeuCys Ser Ala Leu Asn Cys Gln Tyr Gln Cys His Glu 1255 1260 1265 ACG CCGTAT GGA GGA GCG TGT TTT TGT CCC CCA GGT TAT ATC ATC AAC 1123 Thr Pro TyrGly Gly Ala Cys Phe Cys Pro Pro Gly Tyr Ile Ile Asn 1270 1275 1280 CACAAT GAC AGC CGT ACC TGT GTT GAG TTT GAT GAT TGC CAG ATA TGG 1171 His AsnAsp Ser Arg Thr Cys Val Glu Phe Asp Asp Cys Gln Ile Trp 1285 1290 12951300 GGA ATT TGT GAC CAG AAG TGT GAA AGC CGA CCT GGC CGT CAC CTG TGC1219 Gly Ile Cys Asp Gln Lys Cys Glu Ser Arg Pro Gly Arg His Leu Cys1305 1310 1315 CAC TGT GAA GAA GGG TAT ATC TTG GAG CGT GGA CAG TAT TGCAAA GCT 1267 His Cys Glu Glu Gly Tyr Ile Leu Glu Arg Gly Gln Tyr Cys LysAla 1320 1325 1330 AAT GAT TCC TTT GGC GAG GCC TCC ATT ATC TTC TCC AATGGT CGG GAT 1315 Asn Asp Ser Phe Gly Glu Ala Ser Ile Ile Phe Ser Asn GlyArg Asp 1335 1340 1345 TTG TTA ATT GGT GAT ATT CAT GGA AGG AGC TTC CGGATC CTA GTG GAG 1363 Leu Leu Ile Gly Asp Ile His Gly Arg Ser Phe Arg IleLeu Val Glu 1350 1355 1360 TCT CAG AAT CGT GGA GTG GCC GTG GGT GTG GCTTTC CAC TAT CAC CTG 1411 Ser Gln Asn Arg Gly Val Ala Val Gly Val Ala PheHis Tyr His Leu 1365 1370 1375 1380 CAA AGA GTT TTT TGG ACA GAC ACC GTGCAA AAT AAG GTT TTT TCA GTT 1459 Gln Arg Val Phe Trp Thr Asp Thr Val GlnAsn Lys Val Phe Ser Val 1385 1390 1395 GAC ATT AAT GGT TTA AAT ATC CAAGAG GTT CTC AAT GTT TCT GTT GAA 1507 Asp Ile Asn Gly Leu Asn Ile Gln GluVal Leu Asn Val Ser Val Glu 1400 1405 1410 ACC CCA GAG AAC CTG GCT GTGGAC TGG GTT AAT AAT AAA ATC TAT CTA 1555 Thr Pro Glu Asn Leu Ala Val AspTrp Val Asn Asn Lys Ile Tyr Leu 1415 1420 1425 GTG GAA ACC AAG GTC AACCGC ATA GAT ATG GTA AAT TTG GAT GGA AGC 1603 Val Glu Thr Lys Val Asn ArgIle Asp Met Val Asn Leu Asp Gly Ser 1430 1435 1440 TAT CGG GTT ACC CTTATA ACT GAA AAC TTG GGG CAT CCT AGA GGA ATT 1651 Tyr Arg Val Thr Leu IleThr Glu Asn Leu Gly His Pro Arg Gly Ile 1445 1450 1455 1460 GCC GTG GACCCA ACT GTT GGT TAT TTA TTT TTC TCA GAT TGG GAG AGC 1699 Ala Val Asp ProThr Val Gly Tyr Leu Phe Phe Ser Asp Trp Glu Ser 1465 1470 1475 CTT TCTGGG GAA CCT AAG CTG GAA AGG GCA TTC ATG GAT GGC AGC AAC 1747 Leu Ser GlyGlu Pro Lys Leu Glu Arg Ala Phe Met Asp Gly Ser Asn 1480 1485 1490 CGTAAA GAC TTG GTG AAA ACA AAG CTG GGA TGG CCT GCT GGG GTA ACT 1795 Arg LysAsp Leu Val Lys Thr Lys Leu Gly Trp Pro Ala Gly Val Thr 1495 1500 1505CTG GAT ATG ATA TCG AAG CGT GTT TAC TGG GTT GAC TCT CGG TTT GAT 1843 LeuAsp Met Ile Ser Lys Arg Val Tyr Trp Val Asp Ser Arg Phe Asp 1510 15151520 TAC ATT GAA ACT GTA ACT TAT GAT GGA ATT CAA AGG AAG ACT GTA GTT1891 Tyr Ile Glu Thr Val Thr Tyr Asp Gly Ile Gln Arg Lys Thr Val Val1525 1530 1535 1540 CAT GGA GGC TCC CTC ATT CCT CAT CCC TTT GGA GTA AGCTTA TTT GAA 1939 His Gly Gly Ser Leu Ile Pro His Pro Phe Gly Val Ser LeuPhe Glu 1545 1550 1555 GGT CAG GTG TTC TTT ACA GAT TGG ACA AAG ATG GCCGTG CTG AAG GCA 1987 Gly Gln Val Phe Phe Thr Asp Trp Thr Lys Met Ala ValLeu Lys Ala 1560 1565 1570 AAC AAG TTC ACA GAG ACC AAC CCA CAA GTG TACTAC CAG GCT TCC CTG 2035 Asn Lys Phe Thr Glu Thr Asn Pro Gln Val Tyr TyrGln Ala Ser Leu 1575 1580 1585 AGG CCC TAT GGA GTG ACT GTT TAC CAT TCCCTC AGA CAG CCC TAT GCT 2083 Arg Pro Tyr Gly Val Thr Val Tyr His Ser LeuArg Gln Pro Tyr Ala 1590 1595 1600 ACC AAT CCG TGT AAA GAT AAC AAT GGGGGC TGT GAG CAG GTC TGT GTT 2131 Thr Asn Pro Cys Lys Asp Asn Asn Gly GlyCys Glu Gln Val Cys Val 1605 1610 1615 1620 CTC AGC CAC AGA ACA GAT AATGAT GGT TTG GGT TTC CGT TGC AAG TGC 2179 Leu Ser His Arg Thr Asp Asn AspGly Leu Gly Phe Arg Cys Lys Cys 1625 1630 1635 ACA TTC GGC TTC CAA CTGGAT ACA GAT GAG CGC CAC TGC ATT GCT GTT 2227 Thr Phe Gly Phe Gln Leu AspThr Asp Glu Arg His Cys Ile Ala Val 1640 1645 1650 CAG AAT TTC CTC ATTTTT TCA TCC CAA GTT GCT ATT CGT GGG ATC CCG 2275 Gln Asn Phe Leu Ile PheSer Ser Gln Val Ala Ile Arg Gly Ile Pro 1655 1660 1665 TTC ACC TTG TCTACC CAG GAA GAT GTC ATG GTT CCA GTT TCG GGG AAT 2323 Phe Thr Leu Ser ThrGln Glu Asp Val Met Val Pro Val Ser Gly Asn 1670 1675 1680 CCT TCT TTCTTT GTC GGG ATT GAT TTT GAC GCC CAG GAC AGC ACT ATC 2371 Pro Ser Phe PheVal Gly Ile Asp Phe Asp Ala Gln Asp Ser Thr Ile 1685 1690 1695 1700 TTTTTT TCA GAT ATG TCA AAA CAC ATG ATT TTT AAG CAA AAG ATT GAT 2419 Phe PheSer Asp Met Ser Lys His Met Ile Phe Lys Gln Lys Ile Asp 1705 1710 1715GGC ACA GGA AGA GAA ATT CTC GCA GCT AAC AGG GTG GAA AAT GTT GAA 2467 GlyThr Gly Arg Glu Ile Leu Ala Ala Asn Arg Val Glu Asn Val Glu 1720 17251730 AGT TTG GCT TTT GAT TGG ATT TCA AAG AAT CTC TAT TGG ACA GAC TCT2515 Ser Leu Ala Phe Asp Trp Ile Ser Lys Asn Leu Tyr Trp Thr Asp Ser1735 1740 1745 CAT TAC AAG AGT ATC AGT GTC ATG AGG CTA GCT GAT AAA ACGAGA CGC 2563 His Tyr Lys Ser Ile Ser Val Met Arg Leu Ala Asp Lys Thr ArgArg 1750 1755 1760 ACA GTA GTT CAG TAT TTA AAT AAC CCA CGG TCG GTG GTAGTT CAT CCT 2611 Thr Val Val Gln Tyr Leu Asn Asn Pro Arg Ser Val Val ValHis Pro 1765 1770 1775 1780 TTT GCC GGG TAT CTA TTC TTC ACT GAT TGG TTCCGT CCT GCT AAA ATT 2659 Phe Ala Gly Tyr Leu Phe Phe Thr Asp Trp Phe ArgPro Ala Lys Ile 1785 1790 1795 ATG AGA GCA TGG AGT GAC GGA TCT CAC CTCTTG CCT GTA ATA AAC ACT 2707 Met Arg Ala Trp Ser Asp Gly Ser His Leu LeuPro Val Ile Asn Thr 1800 1805 1810 ACT CTT GGA TGG CCC AAT GGC TTG GCCATC GAT TGG GCT GCT TCA CGA 2755 Thr Leu Gly Trp Pro Asn Gly Leu Ala IleAsp Trp Ala Ala Ser Arg 1815 1820 1825 TTG TAC TGG GTA GAT GCC TAT TTTGAT AAA ATT GAG CAC AGC ACC TTT 2803 Leu Tyr Trp Val Asp Ala Tyr Phe AspLys Ile Glu His Ser Thr Phe 1830 1835 1840 GAT GGT TTA GAC AGA AGA AGACTG GGC CAT ATA GAG CAG ATG ACA CAT 2851 Asp Gly Leu Asp Arg Arg Arg LeuGly His Ile Glu Gln Met Thr His 1845 1850 1855 1860 CCG TTT GGA CTT GCCATC TTT GGA GAG CAT TTA TTT TTT ACT GAC TGG 2899 Pro Phe Gly Leu Ala IlePhe Gly Glu His Leu Phe Phe Thr Asp Trp 1865 1870 1875 AGA CTG GGT GCCATT ATT CGA GTC AGG AAA GCA GAT GGT GGA GAA ATG 2947 Arg Leu Gly Ala IleIle Arg Val Arg Lys Ala Asp Gly Gly Glu Met 1880 1885 1890 ACA GTT ATCCGA AGT GGC ATT GCT TAC ATA CTG CAT TTG AAA TCG TAT 2995 Thr Val Ile ArgSer Gly Ile Ala Tyr Ile Leu His Leu Lys Ser Tyr 1895 1900 1905 GAT GTCAAC ATC CAG ACT GGT TCT AAC GCC TGT AAT CAA CCC ACG CAT 3043 Asp Val AsnIle Gln Thr Gly Ser Asn Ala Cys Asn Gln Pro Thr His 1910 1915 1920 CCTAAC GGT GAC TGC AGC CAC TTC TGC TTC CCG GTG CCA AAT TTC CAG 3091 Pro AsnGly Asp Cys Ser His Phe Cys Phe Pro Val Pro Asn Phe Gln 1925 1930 19351940 CGA GTG TGT GGG TGC CCT TAT GGA ATG AGG CTG GCT TCC AAT CAC TTG3139 Arg Val Cys Gly Cys Pro Tyr Gly Met Arg Leu Ala Ser Asn His Leu1945 1950 1955 ACA TGC GAG GGG GAC CCA ACC AAT GAA CCA CCC ACG GAG CAGTGT GGC 3187 Thr Cys Glu Gly Asp Pro Thr Asn Glu Pro Pro Thr Glu Gln CysGly 1960 1965 1970 TTA TTT TCC TTC CCC TGT AAA AAT GGC AGA TGT GTG CCCAAT TAC TAT 3235 Leu Phe Ser Phe Pro Cys Lys Asn Gly Arg Cys Val Pro AsnTyr Tyr 1975 1980 1985 CTC TGT GAT GGA GTC GAT GAT TGT CAT GAT AAC AGTGAT GAG CAA CTA 3283 Leu Cys Asp Gly Val Asp Asp Cys His Asp Asn Ser AspGlu Gln Leu 1990 1995 2000 TGT GGC ACA CTT AAT AAT ACC TGT TCA TCT TCGGCG TTC ACC TGT GGC 3331 Cys Gly Thr Leu Asn Asn Thr Cys Ser Ser Ser AlaPhe Thr Cys Gly 2005 2010 2015 2020 CAT GGG GAG TGC ATT CCT GCA CAC TGGCGC TGT GAC AAA CGC AAC GAC 3379 His Gly Glu Cys Ile Pro Ala His Trp ArgCys Asp Lys Arg Asn Asp 2025 2030 2035 TGT GTG GAT GGC AGT GAT GAG CACAAC TGC CCC ACC CAC GCA CCT GCT 3427 Cys Val Asp Gly Ser Asp Glu His AsnCys Pro Thr His Ala Pro Ala 2040 2045 2050 TCC TGC CTT GAC ACC CAA TACACC TGT GAT AAT CAC CAG TGT ATC TCA 3475 Ser Cys Leu Asp Thr Gln Tyr ThrCys Asp Asn His Gln Cys Ile Ser 2055 2060 2065 AAG AAC TGG GTC TGT GACACA GAC AAT GAT TGT GGG GAT GGA TCT GAT 3523 Lys Asn Trp Val Cys Asp ThrAsp Asn Asp Cys Gly Asp Gly Ser Asp 2070 2075 2080 GAA AAG AAC TGC AATTCG ACA GAG ACA TGC CAA CCT AGT CAG TTT AAT 3571 Glu Lys Asn Cys Asn SerThr Glu Thr Cys Gln Pro Ser Gln Phe Asn 2085 2090 2095 2100 TGC CCC AATCAT CGA TGT ATT GAC CTA TCG TTT GTC TGT GAT GGT GAC 3619 Cys Pro Asn HisArg Cys Ile Asp Leu Ser Phe Val Cys Asp Gly Asp 2105 2110 2115 AAG GATTGT GTT GAT GGA TCT GAT GAG GTT GGT TGT GTA TTA AAC TGT 3667 Lys Asp CysVal Asp Gly Ser Asp Glu Val Gly Cys Val Leu Asn Cys 2120 2125 2130 ACTGCT TCT CAA TTC AAG TGT GCC AGT GGG GAT AAA TGT ATT GGC GTC 3715 Thr AlaSer Gln Phe Lys Cys Ala Ser Gly Asp Lys Cys Ile Gly Val 2135 2140 2145ACA AAT CGT TGT GAT GGT GTT TTT GAT TGC AGT GAC AAC TCG GAT GAA 3763 ThrAsn Arg Cys Asp Gly Val Phe Asp Cys Ser Asp Asn Ser Asp Glu 2150 21552160 GCG GGC TGT CCA ACC AGG CCT CCT GGT ATG TGC CAC TCA GAT GAA TTT3811 Ala Gly Cys Pro Thr Arg Pro Pro Gly Met Cys His Ser Asp Glu Phe2165 2170 2175 2180 CAG TGC CAA GAA GAT GGT ATC TGC ATC CCG AAC TTC TGGGAA TGT GAT 3859 Gln Cys Gln Glu Asp Gly Ile Cys Ile Pro Asn Phe Trp GluCys Asp 2185 2190 2195 GGG CAT CCA GAC TGC CTC TAT GGA TCT GAT GAG CACAAT GCC TGT GTC 3907 Gly His Pro Asp Cys Leu Tyr Gly Ser Asp Glu His AsnAla Cys Val 2200 2205 2210 CCC AAG ACT TGC CCT TCA TCA TAT TTC CAC TGTGAC AAC GGA AAC TGC 3955 Pro Lys Thr Cys Pro Ser Ser Tyr Phe His Cys AspAsn Gly Asn Cys 2215 2220 2225 ATC CAC AGG GCA TGG CTC TGT GAT CGG GACAAT GAC TGC GGG GAT ATG 4003 Ile His Arg Ala Trp Leu Cys Asp Arg Asp AsnAsp Cys Gly Asp Met 2230 2235 2240 AGT GAT GAG AAG GAC TGC CCT ACT CAGCCC TTT CGC TGT CCT AGT TGG 4051 Ser Asp Glu Lys Asp Cys Pro Thr Gln ProPhe Arg Cys Pro Ser Trp 2245 2250 2255 2260 CAA TGG CAG TGT CTT GGC CATAAC ATC TGT GTG AAT CTG AGT GTA GTG 4099 Gln Trp Gln Cys Leu Gly His AsnIle Cys Val Asn Leu Ser Val Val 2265 2270 2275 TGT GAT GGC ATC TTT GACTGC CCC AAT GGG ACA GAT GAG TCC CCA CTT 4147 Cys Asp Gly Ile Phe Asp CysPro Asn Gly Thr Asp Glu Ser Pro Leu 2280 2285 2290 TGC AAT GGG AAC AGCTGC TCA GAT TTC AAT GGT GGT TGT ACT CAC GAG 4195 Cys Asn Gly Asn Ser CysSer Asp Phe Asn Gly Gly Cys Thr His Glu 2295 2300 2305 TGT GTT CAA GAGCCC TTT GGG GCT AAA TGC CTA TGT CCA TTG GGA TTC 4243 Cys Val Gln Glu ProPhe Gly Ala Lys Cys Leu Cys Pro Leu Gly Phe 2310 2315 2320 TTA CTT GCCAAT GAT TCT AAG ACC TGT GAA GAC ATA GAT GAA TGT GAT 4291 Leu Leu Ala AsnAsp Ser Lys Thr Cys Glu Asp Ile Asp Glu Cys Asp 2325 2330 2335 2340 ATTCTA GGC TCT TGT AGC CAG CAC TGT TAC AAT ATG AGA GGT TCT TTC 4339 Ile LeuGly Ser Cys Ser Gln His Cys Tyr Asn Met Arg Gly Ser Phe 2345 2350 2355CGG TGC TCG TGT GAT ACA GGC TAC ATG TTA GAA AGT GAT GGG AGG ACT 4387 ArgCys Ser Cys Asp Thr Gly Tyr Met Leu Glu Ser Asp Gly Arg Thr 2360 23652370 TGC AAA GTT ACA GCA TCT GAG AGT CTG CTG TTA CTT GTG GCA AGT CAG4435 Cys Lys Val Thr Ala Ser Glu Ser Leu Leu Leu Leu Val Ala Ser Gln2375 2380 2385 AAC AAA ATT ATT GCC GAC AGT GTC ACC TCC CAG GTC CAC AATATC TAT 4483 Asn Lys Ile Ile Ala Asp Ser Val Thr Ser Gln Val His Asn IleTyr 2390 2395 2400 TCA TTG GTC GAG AAT GGT TCT TAC ATT GTA GCT GTT GATTTT GAT TCA 4531 Ser Leu Val Glu Asn Gly Ser Tyr Ile Val Ala Val Asp PheAsp Ser 2405 2410 2415 2420 ATT AGT GGT CGT ATC TTT TGG TCT GAT GCA ACTCAG GGT AAA ACC TGG 4579 Ile Ser Gly Arg Ile Phe Trp Ser Asp Ala Thr GlnGly Lys Thr Trp 2425 2430 2435 AGT GCG TTT CAA AAT GGA ACG GAC AGA AGAGTG GTA TTT GAC AGT AGC 4627 Ser Ala Phe Gln Asn Gly Thr Asp Arg Arg ValVal Phe Asp Ser Ser 2440 2445 2450 ATC ATC TTG ACT GAA ACT ATT GCA ATAGAT TGG GTA GGT CGT AAT CTT 4675 Ile Ile Leu Thr Glu Thr Ile Ala Ile AspTrp Val Gly Arg Asn Leu 2455 2460 2465 TAC TGG ACA GAC TAT GCT CTG GAAACA ATT GAA GTC TCC AAA ATT GAT 4723 Tyr Trp Thr Asp Tyr Ala Leu Glu ThrIle Glu Val Ser Lys Ile Asp 2470 2475 2480 GGG AGC CAC AGG ACT GTG CTGATT AGT AAA AAC CTA ACA AAT CCA AGA 4771 Gly Ser His Arg Thr Val Leu IleSer Lys Asn Leu Thr Asn Pro Arg 2485 2490 2495 2500 GGA CTA GCA TTA GATCCC AGA ATG AAT GAG CAT CTA CTG TTC TGG TCT 4819 Gly Leu Ala Leu Asp ProArg Met Asn Glu His Leu Leu Phe Trp Ser 2505 2510 2515 GAC TGG GGC CACCAC CCT CGC ATC GAG CGA GCC AGC ATG GAC GGC AGC 4867 Asp Trp Gly His HisPro Arg Ile Glu Arg Ala Ser Met Asp Gly Ser 2520 2525 2530 ATG CGC ACTGTC ATT GTC CAG GAC AAG ATC TTC TGG CCC TGC GGC TTA 4915 Met Arg Thr ValIle Val Gln Asp Lys Ile Phe Trp Pro Cys Gly Leu 2535 2540 2545 ACT ATTGAC TAC CCC AAC AGA CTG CTC TAC TTC ATG GAC TCC TAT CTT 4963 Thr Ile AspTyr Pro Asn Arg Leu Leu Tyr Phe Met Asp Ser Tyr Leu 2550 2555 2560 GATTAC ATG GAC TTT TGC GAT TAT AAT GGA CAC CAT CGG AGA CAG GTG 5011 Asp TyrMet Asp Phe Cys Asp Tyr Asn Gly His His Arg Arg Gln Val 2565 2570 25752580 ATA GCC AGT GAT TTG ATT ATA CGG CAC CCC TAT GCC CTA ACT CTC TTT5059 Ile Ala Ser Asp Leu Ile Ile Arg His Pro Tyr Ala Leu Thr Leu Phe2585 2590 2595 GAA GAC TCT GTG TAC TGG ACT GAC CGT GCT ACT CGT CGG GTTATG CGA 5107 Glu Asp Ser Val Tyr Trp Thr Asp Arg Ala Thr Arg Arg Val MetArg 2600 2605 2610 GCC AAC AAG TGG CAT GGA GGG AAC CAG TCA GTT GTA ATGTAT AAT ATT 5155 Ala Asn Lys Trp His Gly Gly Asn Gln Ser Val Val Met TyrAsn Ile 2615 2620 2625 CAA TGG CCC CTT GGG ATT GTT GCG GTT CAT CCT TCGAAA CAA CCA AAT 5203 Gln Trp Pro Leu Gly Ile Val Ala Val His Pro Ser LysGln Pro Asn 2630 2635 2640 TCC GTG AAT CCA TGT GCC TTT TCC CGC TGC AGCCAT CTC TGC CTG CTT 5251 Ser Val Asn Pro Cys Ala Phe Ser Arg Cys Ser HisLeu Cys Leu Leu 2645 2650 2655 2660 TCC TCA CAG GGG CCT CAT TTT TAC TCCTGT GTT TGT CCT TCA GGA TGG 5299 Ser Ser Gln Gly Pro His Phe Tyr Ser CysVal Cys Pro Ser Gly Trp 2665 2670 2675 AGT CTG TCT CCT GAT CTC CTG AATTGC TTG AGA GAT GAT CAA CCT TTC 5347 Ser Leu Ser Pro Asp Leu Leu Asn CysLeu Arg Asp Asp Gln Pro Phe 2680 2685 2690 TTA ATA ACT GTA AGG CAA CATATA ATT TTT GGA ATC TCC CTT AAT CCT 5395 Leu Ile Thr Val Arg Gln His IleIle Phe Gly Ile Ser Leu Asn Pro 2695 2700 2705 GAG GTG AAG AGC AAT GATGCT ATG GTC CCC ATA GCA GGG ATA CAG AAT 5443 Glu Val Lys Ser Asn Asp AlaMet Val Pro Ile Ala Gly Ile Gln Asn 2710 2715 2720 GGT TTA GAT GTT GAATTT GAT GAT GCT GAG CAA TAC ATC TAT TGG GTT 5491 Gly Leu Asp Val Glu PheAsp Asp Ala Glu Gln Tyr Ile Tyr Trp Val 2725 2730 2735 2740 GAA AAT CCAGGT GAA ATT CAC AGA GTG AAG ACA GAT GGC ACC AAC AGG 5539 Glu Asn Pro GlyGlu Ile His Arg Val Lys Thr Asp Gly Thr Asn Arg 2745 2750 2755 ACA GTATTT GCT TCT ATA TCT ATG GTG GGG CCT TCT ATG AAC CTG GCC 5587 Thr Val PheAla Ser Ile Ser Met Val Gly Pro Ser Met Asn Leu Ala 2760 2765 2770 TTAGAT TGG ATT TCA AGA AAC CTT TAT TCT ACC AAT CCT AGA ACT CAG 5635 Leu AspTrp Ile Ser Arg Asn Leu Tyr Ser Thr Asn Pro Arg Thr Gln 2775 2780 2785TCA ATC GAG GTT TTG ACA CTC CAC GGA GAT ATC AGA TAC AGA AAA ACA 5683 SerIle Glu Val Leu Thr Leu His Gly Asp Ile Arg Tyr Arg Lys Thr 2790 27952800 TTG ATT GCC AAT GAT GGG ACA GCT CTT GGA GTT GGC TTT CCA ATT GGC5731 Leu Ile Ala Asn Asp Gly Thr Ala Leu Gly Val Gly Phe Pro Ile Gly2805 2810 2815 2820 ATA ACT GTT GAT CCT GCT CGT GGG AAG CTG TAC TGG TCAGAC CAA GGA 5779 Ile Thr Val Asp Pro Ala Arg Gly Lys Leu Tyr Trp Ser AspGln Gly 2825 2830 2835 ACT GAC AGT GGG GTT CCT GCC AAG ATC GCC AGT GCTAAC ATG GAT GGC 5827 Thr Asp Ser Gly Val Pro Ala Lys Ile Ala Ser Ala AsnMet Asp Gly 2840 2845 2850 ACA TCT GTG AAA ACT CTC TTT ACT GGG AAC CTCGAA CAC CTG GAG TGT 5875 Thr Ser Val Lys Thr Leu Phe Thr Gly Asn Leu GluHis Leu Glu Cys 2855 2860 2865 GTC ACT CTT GAC ATC GAA GAG CAG AAA CTCTAC TGG GCA GTC ACT GGA 5923 Val Thr Leu Asp Ile Glu Glu Gln Lys Leu TyrTrp Ala Val Thr Gly 2870 2875 2880 AGA GGA GTG ATT GAA AGA GGA AAC GTGGAT GGA ACA GAT CGG ATG ATC 5971 Arg Gly Val Ile Glu Arg Gly Asn Val AspGly Thr Asp Arg Met Ile 2885 2890 2895 2900 CTG GTA CAC CAG CTT TCC CACCCC TGG GGA ATT GCA GTC CAT GAT TCT 6019 Leu Val His Gln Leu Ser His ProTrp Gly Ile Ala Val His Asp Ser 2905 2910 2915 TTC CTT TAT TAT ACT GATGAA CAG TAT GAG GTC ATT GAA AGA GTT GAT 6067 Phe Leu Tyr Tyr Thr Asp GluGln Tyr Glu Val Ile Glu Arg Val Asp 2920 2925 2930 AAG GCC ACT GGG GCCAAC AAA ATA GTC TTG AGA GAT AAT GTT CCA AAT 6115 Lys Ala Thr Gly Ala AsnLys Ile Val Leu Arg Asp Asn Val Pro Asn 2935 2940 2945 CTG AGG GGT CTTCAA GTT TAT CAC AGA CGC AAT GCC GCC GAA TCC TCA 6163 Leu Arg Gly Leu GlnVal Tyr His Arg Arg Asn Ala Ala Glu Ser Ser 2950 2955 2960 AAT GGC TGTAGC AAC AAC ATG AAT GCC TGT CAG CAG ATT TGC CTG CCT 6211 Asn Gly Cys SerAsn Asn Met Asn Ala Cys Gln Gln Ile Cys Leu Pro 2965 2970 2975 2980 GTACCA GGA GGA TTG TTT TCC TGC GCC TGT GCC ACT GGA TTT AAA CTC 6259 Val ProGly Gly Leu Phe Ser Cys Ala Cys Ala Thr Gly Phe Lys Leu 2985 2990 2995AAT CCT GAT AAT CGG TCC TGC TCT CCA TAT AAC TCT TTC ATT GTT GTT 6307 AsnPro Asp Asn Arg Ser Cys Ser Pro Tyr Asn Ser Phe Ile Val Val 3000 30053010 TCA ATG CTG TCT GCA ATC AGA GGC TTT AGC TTG GAA TTG TCA GAT CAT6355 Ser Met Leu Ser Ala Ile Arg Gly Phe Ser Leu Glu Leu Ser Asp His3015 3020 3025 TCA GAA ACC ATG GTG CCG GTG GCA GGC CAA GGA CGA AAC GCACTG CAT 6403 Ser Glu Thr Met Val Pro Val Ala Gly Gln Gly Arg Asn Ala LeuHis 3030 3035 3040 GTG GAT GTG GAT GTG TCC TCT GGC TTT ATT TAT TGG TGTGAT TTT AGC 6451 Val Asp Val Asp Val Ser Ser Gly Phe Ile Tyr Trp Cys AspPhe Ser 3045 3050 3055 3060 AGC TCA GTG GCA TCT GAT AAT GCG ATC CGT AGAATT AAA CCA GAT GGA 6499 Ser Ser Val Ala Ser Asp Asn Ala Ile Arg Arg IleLys Pro Asp Gly 3065 3070 3075 TCT TCT CTG ATG AAC ATT GTG ACA CAT GGAATA GGA GAA AAT GGA GTC 6547 Ser Ser Leu Met Asn Ile Val Thr His Gly IleGly Glu Asn Gly Val 3080 3085 3090 CGG GGT ATT GCA GTG GAT TGG GTA GCAGGA AAT CTT TAT TTC ACC AAT 6595 Arg Gly Ile Ala Val Asp Trp Val Ala GlyAsn Leu Tyr Phe Thr Asn 3095 3100 3105 GCC TTT GTT TCT GAA ACA CTG ATAGAA GTT CTG CGG ATC AAT ACT ACT 6643 Ala Phe Val Ser Glu Thr Leu Ile GluVal Leu Arg Ile Asn Thr Thr 3110 3115 3120 TAC CGC CGT GTT CTT CTT AAAGTC ACA GTG GAC ATG CCT AGG CAT ATT 6691 Tyr Arg Arg Val Leu Leu Lys ValThr Val Asp Met Pro Arg His Ile 3125 3130 3135 3140 GTT GTA GAT CCC AAGAAC AGA TAC CTC TTC TGG GCT GAC TAT GGG CAG 6739 Val Val Asp Pro Lys AsnArg Tyr Leu Phe Trp Ala Asp Tyr Gly Gln 3145 3150 3155 AGA CCA AAG ATTGAG CGT TCT TTC CTT GAC TGT ACC AAT CGA ACA GTG 6787 Arg Pro Lys Ile GluArg Ser Phe Leu Asp Cys Thr Asn Arg Thr Val 3160 3165 3170 CTT GTG TCAGAG GGC ATT GTC ACA CCA CGG GGC TTG GCA GTG GAC CGA 6835 Leu Val Ser GluGly Ile Val Thr Pro Arg Gly Leu Ala Val Asp Arg 3175 3180 3185 AGT GATGGC TAC GTT TAT TGG GTT GAT GAT TCT TTA GAT ATA ATT GCA 6883 Ser Asp GlyTyr Val Tyr Trp Val Asp Asp Ser Leu Asp Ile Ile Ala 3190 3195 3200 AGGATT CGT ATC AAT GGA GAG AAC TCT GAA GTG ATT CGT TAT GGC AGT 6931 Arg IleArg Ile Asn Gly Glu Asn Ser Glu Val Ile Arg Tyr Gly Ser 3205 3210 32153220 CGT TAC CCA ACT CCT TAT GGC ATC ACT GTT TTT GAA AAT TCT ATC ATA6979 Arg Tyr Pro Thr Pro Tyr Gly Ile Thr Val Phe Glu Asn Ser Ile Ile3225 3230 3235 TGG GTA GAT AGG AAT TTG AAA AAG ATC TTC CAA GCC AGC AAGGAA CCA 7027 Trp Val Asp Arg Asn Leu Lys Lys Ile Phe Gln Ala Ser Lys GluPro 3240 3245 3250 GAG AAC ACA GAG CCA CCC ACA GTG ATA AGA GAC AAT ATCAAC TGG CTA 7075 Glu Asn Thr Glu Pro Pro Thr Val Ile Arg Asp Asn Ile AsnTrp Leu 3255 3260 3265 AGA GAT GTG ACC ATC TTT GAC AAG CAA GTC CAG CCCCGG TCA CCA GCA 7123 Arg Asp Val Thr Ile Phe Asp Lys Gln Val Gln Pro ArgSer Pro Ala 3270 3275 3280 GAG GTC AAC AAC AAC CCT TGC TTG GAA AAC AATGGT GGG TGC TCT CAT 7171 Glu Val Asn Asn Asn Pro Cys Leu Glu Asn Asn GlyGly Cys Ser His 3285 3290 3295 3300 CTC TGC TTT GCT CTG CCT GGA TTG CACACC CCA AAA TGT GAC TGT GCC 7219 Leu Cys Phe Ala Leu Pro Gly Leu His ThrPro Lys Cys Asp Cys Ala 3305 3310 3315 TTT GGG ACC CTG CAA AGT GAT GGCAAG AAT TGT GCC ATT TCA ACA GAA 7267 Phe Gly Thr Leu Gln Ser Asp Gly LysAsn Cys Ala Ile Ser Thr Glu 3320 3325 3330 AAT TTC CTC ATC TTT GCC TTGTCT AAT TCC TTG AGA AGC TTA CAC TTG 7315 Asn Phe Leu Ile Phe Ala Leu SerAsn Ser Leu Arg Ser Leu His Leu 3335 3340 3345 GAC CCT GAA AAC CAT AGCCCA CCT TTC CAA ACA ATA AAT GTG GAA AGA 7363 Asp Pro Glu Asn His Ser ProPro Phe Gln Thr Ile Asn Val Glu Arg 3350 3355 3360 ACT GTC ATG TCT CTAGAC TAT GAC AGT GTA AGT GAT AGA ATC TAC TTC 7411 Thr Val Met Ser Leu AspTyr Asp Ser Val Ser Asp Arg Ile Tyr Phe 3365 3370 3375 3380 ACA CAA AATTTA GCC TCT GGA GTT GGA CAG ATT TCC TAT GCC ACC CTG 7459 Thr Gln Asn LeuAla Ser Gly Val Gly Gln Ile Ser Tyr Ala Thr Leu 3385 3390 3395 TCT TCAGGG ATC CAT ACT CCA ACT GTC ATT GCT TCA GGT ATA GGG ACT 7507 Ser Ser GlyIle His Thr Pro Thr Val Ile Ala Ser Gly Ile Gly Thr 3400 3405 3410 GCTGAT GGC ATT GCC TTT GAC TGG ATT ACT AGA AGA ATT TAT TAC AGT 7555 Ala AspGly Ile Ala Phe Asp Trp Ile Thr Arg Arg Ile Tyr Tyr Ser 3415 3420 3425GAC TAC CTC AAC CAG ATG ATT AAT TCC ATG GCT GAA GAT GGG TCT AAC 7603 AspTyr Leu Asn Gln Met Ile Asn Ser Met Ala Glu Asp Gly Ser Asn 3430 34353440 CGC ACT GTG ATA GCC CGC GTT CCA AAA CCA AGA GCA ATT GTG TTA GAT7651 Arg Thr Val Ile Ala Arg Val Pro Lys Pro Arg Ala Ile Val Leu Asp3445 3450 3455 3460 CCC TGC CAA GGG TAC CTG TAC TGG GCT GAC TGG GAT ACACAT GCC AAA 7699 Pro Cys Gln Gly Tyr Leu Tyr Trp Ala Asp Trp Asp Thr HisAla Lys 3465 3470 3475 ATC GAG AGA GCC ACA TTG GGA GGA AAC TTC CGG GTACCC ATT GTG AAC 7747 Ile Glu Arg Ala Thr Leu Gly Gly Asn Phe Arg Val ProIle Val Asn 3480 3485 3490 AGC AGT CTG GTC ATG CCC AGT GGG CTG ACT CTGGAC TAT GAA GAG GAC 7795 Ser Ser Leu Val Met Pro Ser Gly Leu Thr Leu AspTyr Glu Glu Asp 3495 3500 3505 CTT CTC TAC TGG GTG GAT GCT AGT CTG CAGAGG ATT GAA CGC AGC ACT 7843 Leu Leu Tyr Trp Val Asp Ala Ser Leu Gln ArgIle Glu Arg Ser Thr 3510 3515 3520 CTG ACG GGC GTG GAT CGT GAA GTC ATTGTC AAT GCA GCC GTT CAT GCT 7891 Leu Thr Gly Val Asp Arg Glu Val Ile ValAsn Ala Ala Val His Ala 3525 3530 3535 3540 TTT GGC TTG ACT CTC TAT GGCCAG TAT ATT TAC TGG ACT GAC TTG TAC 7939 Phe Gly Leu Thr Leu Tyr Gly GlnTyr Ile Tyr Trp Thr Asp Leu Tyr 3545 3550 3555 ACA CAA AGA ATT TAC CGAGCT AAC AAA TAT GAC GGG TCA GGT CAG ATT 7987 Thr Gln Arg Ile Tyr Arg AlaAsn Lys Tyr Asp Gly Ser Gly Gln Ile 3560 3565 3570 GCA ATG ACC ACA AATTTG CTC TCC CAG CCC AGG GGA ATC AAC ACT GTT 8035 Ala Met Thr Thr Asn LeuLeu Ser Gln Pro Arg Gly Ile Asn Thr Val 3575 3580 3585 GTG AAG AAC CAGAAA CAA CAG TGT AAC AAT CCT TGT GAA CAG TTT AAT 8083 Val Lys Asn Gln LysGln Gln Cys Asn Asn Pro Cys Glu Gln Phe Asn 3590 3595 3600 GGG GGC TGCAGC CAT ATC TGT GCA CCA GGT CCA AAT GGT GCC GAG TGC 8131 Gly Gly Cys SerHis Ile Cys Ala Pro Gly Pro Asn Gly Ala Glu Cys 3605 3610 3615 3620 CAGTGT CCA CAT GAG GGC AAC TGG TAT TTG GCC AAC AAC AGG AAG CAC 8179 Gln CysPro His Glu Gly Asn Trp Tyr Leu Ala Asn Asn Arg Lys His 3625 3630 3635TGC ATT GTG GAC AAT GGT GAA CGA TGT GGT GCA TCT TCC TTC ACC TGC 8227 CysIle Val Asp Asn Gly Glu Arg Cys Gly Ala Ser Ser Phe Thr Cys 3640 36453650 TCC AAT GGG CGC TGC ATC TCG GAA GAG TGG AAG TGT GAT AAT GAC AAC8275 Ser Asn Gly Arg Cys Ile Ser Glu Glu Trp Lys Cys Asp Asn Asp Asn3655 3660 3665 GAC TGT GGG GAT GGC AGT GAT GAG ATG GAA AGT GTC TGT GCACTT CAC 8323 Asp Cys Gly Asp Gly Ser Asp Glu Met Glu Ser Val Cys Ala LeuHis 3670 3675 3680 ACC TGC TCA CCG ACA GCC TTC ACC TGT GCC AAT GGG CGATGT GTC CAA 8371 Thr Cys Ser Pro Thr Ala Phe Thr Cys Ala Asn Gly Arg CysVal Gln 3685 3690 3695 3700 TAC TCT TAC CGC TGT GAT TAC TAC AAT GAC TGTGGT GAT GGC AGT GAT 8419 Tyr Ser Tyr Arg Cys Asp Tyr Tyr Asn Asp Cys GlyAsp Gly Ser Asp 3705 3710 3715 GAG GCA GGG TGC CTG TTC AGG GAC TGC AATGCC ACC ACG GAG TTT ATG 8467 Glu Ala Gly Cys Leu Phe Arg Asp Cys Asn AlaThr Thr Glu Phe Met 3720 3725 3730 TGC AAT AAC AGA AGG TGC ATA CCT CGTGAG TTT ATC TGC AAT GGT GTA 8515 Cys Asn Asn Arg Arg Cys Ile Pro Arg GluPhe Ile Cys Asn Gly Val 3735 3740 3745 GAC AAC TGC CAT GAT AAT AAC ACTTCA GAT GAG AAA AAT TGC CCT GAT 8563 Asp Asn Cys His Asp Asn Asn Thr SerAsp Glu Lys Asn Cys Pro Asp 3750 3755 3760 CGC ACT TGC CAG TCT GGA TACACA AAA TGT CAT AAT TCA AAT ATT TGT 8611 Arg Thr Cys Gln Ser Gly Tyr ThrLys Cys His Asn Ser Asn Ile Cys 3765 3770 3775 3780 ATT CCT CGC GTT TATTTG TGT GAC GGA GAC AAT GAC TGT GGA GAT AAC 8659 Ile Pro Arg Val Tyr LeuCys Asp Gly Asp Asn Asp Cys Gly Asp Asn 3785 3790 3795 AGT GAT GAA AACCCT ACT TAT TGC ACC ACT CAC ACA TGC AGC AGC AGT 8707 Ser Asp Glu Asn ProThr Tyr Cys Thr Thr His Thr Cys Ser Ser Ser 3800 3805 3810 GAG TTC CAATGC GCA TCT GGG CGC TGT ATT CCT CAA CAT TGG TAT TGT 8755 Glu Phe Gln CysAla Ser Gly Arg Cys Ile Pro Gln His Trp Tyr Cys 3815 3820 3825 GAT CAAGAA ACA GAT TGT TTT GAT GCC TCT GAT GAA CCT GCC TCT TGT 8803 Asp Gln GluThr Asp Cys Phe Asp Ala Ser Asp Glu Pro Ala Ser Cys 3830 3835 3840 GGTCAC TCT GAG CGA ACA TGC CTA GCT GAT GAG TTC AAG TGT GAT GGT 8851 Gly HisSer Glu Arg Thr Cys Leu Ala Asp Glu Phe Lys Cys Asp Gly 3845 3850 38553860 GGG AGG TGC ATC CCA AGC GAA TGG ATC TGT GAC GGT GAT AAT GAC TGT8899 Gly Arg Cys Ile Pro Ser Glu Trp Ile Cys Asp Gly Asp Asn Asp Cys3865 3870 3875 GGG GAT ATG AGT GAC GAG GAT AAA AGG CAC CAG TGT CAG AATCAA AAC 8947 Gly Asp Met Ser Asp Glu Asp Lys Arg His Gln Cys Gln Asn GlnAsn 3880 3885 3890 TGC TCG GAT TCC GAG TTT CTC TGT GTA AAT GAC AGA CCTCCG GAC AGG 8995 Cys Ser Asp Ser Glu Phe Leu Cys Val Asn Asp Arg Pro ProAsp Arg 3895 3900 3905 AGG TGC ATT CCC CAG TCT TGG GTC TGT GAT GGC GATGTG GAT TGT ACT 9043 Arg Cys Ile Pro Gln Ser Trp Val Cys Asp Gly Asp ValAsp Cys Thr 3910 3915 3920 GAC GGC TAC GAT GAG AAT CAG AAT TGC ACC AGGAGA ACT TGC TCT GAA 9091 Asp Gly Tyr Asp Glu Asn Gln Asn Cys Thr Arg ArgThr Cys Ser Glu 3925 3930 3935 3940 AAT GAA TTC ACC TGT GGT TAC GGA CTGTGT ATC CCA AAG ATA TTC AGG 9139 Asn Glu Phe Thr Cys Gly Tyr Gly Leu CysIle Pro Lys Ile Phe Arg 3945 3950 3955 TGT GAC CGG CAC AAT GAC TGT GGTGAC TAT AGC GAC GAG AGG GGC TGC 9187 Cys Asp Arg His Asn Asp Cys Gly AspTyr Ser Asp Glu Arg Gly Cys 3960 3965 3970 TTA TAC CAG ACT TGC CAA CAGAAT CAG TTT ACC TGT CAG AAC GGG CGC 9235 Leu Tyr Gln Thr Cys Gln Gln AsnGln Phe Thr Cys Gln Asn Gly Arg 3975 3980 3985 TGC ATT AGT AAA ACC TTCGTC TGT GAT GAG GAT AAT GAC TGT GGA GAC 9283 Cys Ile Ser Lys Thr Phe ValCys Asp Glu Asp Asn Asp Cys Gly Asp 3990 3995 4000 GGA TCT GAT GAG CTGATG CAC CTG TGC CAC ACC CCA GAA CCC ACG TGT 9331 Gly Ser Asp Glu Leu MetHis Leu Cys His Thr Pro Glu Pro Thr Cys 4005 4010 4015 4020 CCA CCT CACGAG TTC AAG TGT GAC AAT GGG CGC TGC ATC GAG ATG ATG 9379 Pro Pro His GluPhe Lys Cys Asp Asn Gly Arg Cys Ile Glu Met Met 4025 4030 4035 AAA CTCTGC AAC CAC CTA GAT GAC TGT TTG GAC AAC AGC GAT GAG AAA 9427 Lys Leu CysAsn His Leu Asp Asp Cys Leu Asp Asn Ser Asp Glu Lys 4040 4045 4050 GGCTGT GGC ATT AAT GAA TGC CAT GAC CCT TCA ATC AGT GGC TGC GAT 9475 Gly CysGly Ile Asn Glu Cys His Asp Pro Ser Ile Ser Gly Cys Asp 4055 4060 4065CAC AAC TGC ACA GAC ACC TTA ACC AGT TTC TAT TGT TCC TGT CGT CCT 9523 HisAsn Cys Thr Asp Thr Leu Thr Ser Phe Tyr Cys Ser Cys Arg Pro 4070 40754080 GGT TAC AAG CTC ATG TCT GAC AAG CGG ACT TGT GTT GAT ATT GAT GAA9571 Gly Tyr Lys Leu Met Ser Asp Lys Arg Thr Cys Val Asp Ile Asp Glu4085 4090 4095 4100 TGC ACA GAG ATG CCT TTT GTC TGT AGC CAG AAG TGT GAGAAT GTA ATA 9619 Cys Thr Glu Met Pro Phe Val Cys Ser Gln Lys Cys Glu AsnVal Ile 4105 4110 4115 GGC TCC TAC ATC TGT AAG TGT GCC CCA GGC TAC CTCCGA GAA CCA GAT 9667 Gly Ser Tyr Ile Cys Lys Cys Ala Pro Gly Tyr Leu ArgGlu Pro Asp 4120 4125 4130 GGA AAG ACC TGC CGG CAA AAC AGT AAC ATC GAACCC TAT CTC ATT TTT 9715 Gly Lys Thr Cys Arg Gln Asn Ser Asn Ile Glu ProTyr Leu Ile Phe 4135 4140 4145 AGC AAC CGT TAC TAT TTG AGA AAT TTA ACTATA GAT GGC TAT TTT TAC 9763 Ser Asn Arg Tyr Tyr Leu Arg Asn Leu Thr IleAsp Gly Tyr Phe Tyr 4150 4155 4160 TCC CTC ATC TTG GAA GGA CTG GAC AATGTT GTG GCA TTA GAT TTT GAC 9811 Ser Leu Ile Leu Glu Gly Leu Asp Asn ValVal Ala Leu Asp Phe Asp 4165 4170 4175 4180 CGA GTA GAG AAG AGA TTG TATTGG ATT GAT ACA CAG AGG CAA GTC ATT 9859 Arg Val Glu Lys Arg Leu Tyr TrpIle Asp Thr Gln Arg Gln Val Ile 4185 4190 4195 GAG AGA ATG TTT CTG AATAAG ACA AAC AAG GAG ACA ATC ATA AAC CAC 9907 Glu Arg Met Phe Leu Asn LysThr Asn Lys Glu Thr Ile Ile Asn His 4200 4205 4210 AGA CTA CCA GCT GCAGAA AGT CTG GCT GTA GAC TGG GTT TCC AGA AAG 9955 Arg Leu Pro Ala Ala GluSer Leu Ala Val Asp Trp Val Ser Arg Lys 4215 4220 4225 CTC TAC TGG TTGGAT GCC CGC CTG GAT GGC CTC TTT GTC TCT GAC CTC 10003 Leu Tyr Trp LeuAsp Ala Arg Leu Asp Gly Leu Phe Val Ser Asp Leu 4230 4235 4240 AAT GGTGGA CAC CGC CGC ATG CTG GCC CAG CAC TGT GTG GAT GCC AAC 10051 Asn GlyGly His Arg Arg Met Leu Ala Gln His Cys Val Asp Ala Asn 4245 4250 42554260 AAC ACC TTC TGC TTT GAT AAT CCC AGA GGA CTT GCC CTT CAC CCT CAA10099 Asn Thr Phe Cys Phe Asp Asn Pro Arg Gly Leu Ala Leu His Pro Gln4265 4270 4275 TAT GGG TAC CTC TAC TGG GCA GAC TGG GGT CAC CGC GCA TACATT GGG 10147 Tyr Gly Tyr Leu Tyr Trp Ala Asp Trp Gly His Arg Ala TyrIle Gly 4280 4285 4290 AGA GTA GGC ATG GAT GGA ACC AAC AAG TCT GTG ATAATC TCC ACC AAG 10195 Arg Val Gly Met Asp Gly Thr Asn Lys Ser Val IleIle Ser Thr Lys 4295 4300 4305 TTA GAG TGG CCT AAT GGC ATC ACC ATT GATTAC ACC AAT GAT CTA CTC 10243 Leu Glu Trp Pro Asn Gly Ile Thr Ile AspTyr Thr Asn Asp Leu Leu 4310 4315 4320 TAC TGG GCA GAT GCC CAC CTG GGTTAC ATA GAG TAC TCT GAT TTG GAG 10291 Tyr Trp Ala Asp Ala His Leu GlyTyr Ile Glu Tyr Ser Asp Leu Glu 4325 4330 4335 4340 GGC CAC CAT CGA CACACG GTG TAT GAT GGG GCA CTG CCT CAC CCT TTC 10339 Gly His His Arg HisThr Val Tyr Asp Gly Ala Leu Pro His Pro Phe 4345 4350 4355 GCT ATT ACCATT TTT GAA GAC ACT ATT TAT TGG ACA GAT TGG AAT ACA 10387 Ala Ile ThrIle Phe Glu Asp Thr Ile Tyr Trp Thr Asp Trp Asn Thr 4360 4365 4370 AGGACA GTG GAA AAG GGA AAC AAA TAT GAT GGA TCA AAT AGA CAG ACA 10435 ArgThr Val Glu Lys Gly Asn Lys Tyr Asp Gly Ser Asn Arg Gln Thr 4375 43804385 CTG GTG AAC ACA ACA CAC AGA CCA TTT GAC ATC CAT GTG TAC CAT CCA10483 Leu Val Asn Thr Thr His Arg Pro Phe Asp Ile His Val Tyr His Pro4390 4395 4400 TAT AGG CAG CCC ATT GTG AGC AAT CCC TGT GGT ACC AAC AATGGT GGC 10531 Tyr Arg Gln Pro Ile Val Ser Asn Pro Cys Gly Thr Asn AsnGly Gly 4405 4410 4415 4420 TGT TCT CAT CTC TGC CTC ATC AAG CCA GGA GGAAAA GGG TTC ACT TGC 10579 Cys Ser His Leu Cys Leu Ile Lys Pro Gly GlyLys Gly Phe Thr Cys 4425 4430 4435 GAG TGT CCA GAT GAC TTC CGC ACC CTTCAA CTG AGT GGC AGC ACC TAC 10627 Glu Cys Pro Asp Asp Phe Arg Thr LeuGln Leu Ser Gly Ser Thr Tyr 4440 4445 4450 TGC ATG CCC ATG TGC TCC AGCACC CAG TTC CTG TGC GCT AAC AAT GAA 10675 Cys Met Pro Met Cys Ser SerThr Gln Phe Leu Cys Ala Asn Asn Glu 4455 4460 4465 AAG TGC ATT CCT ATCTGG TGG AAA TGT GAT GGA CAG AAA GAC TGC TCA 10723 Lys Cys Ile Pro IleTrp Trp Lys Cys Asp Gly Gln Lys Asp Cys Ser 4470 4475 4480 GAT GGC TCTGAT GAA CTG GCC CTT TGC CCG CAG CGC TTC TGC CGA CTG 10771 Asp Gly SerAsp Glu Leu Ala Leu Cys Pro Gln Arg Phe Cys Arg Leu 4485 4490 4495 4500GGA CAG TTC CAG TGC AGT GAC GGC AAC TGC ACC AGC CCG CAG ACT TTA 10819Gly Gln Phe Gln Cys Ser Asp Gly Asn Cys Thr Ser Pro Gln Thr Leu 45054510 4515 TGC AAT GCT CAC CAA AAT TGC CCT GAT GGG TCT GAT GAA GAC CGTCTT 10867 Cys Asn Ala His Gln Asn Cys Pro Asp Gly Ser Asp Glu Asp ArgLeu 4520 4525 4530 CTT TGT GAG AAT CAC CAC TGT GAC TCC AAT GAA TGG CAGTGC GCC AAC 10915 Leu Cys Glu Asn His His Cys Asp Ser Asn Glu Trp GlnCys Ala Asn 4535 4540 4545 AAA CGT TGC ATC CCA GAA TCC TGG CAG TGT GACACA TTT AAC GAC TGT 10963 Lys Arg Cys Ile Pro Glu Ser Trp Gln Cys AspThr Phe Asn Asp Cys 4550 4555 4560 GAG GAT AAC TCA GAT GAA GAC AGT TCCCAC TGT GCC AGC AGG ACC TGC 11011 Glu Asp Asn Ser Asp Glu Asp Ser SerHis Cys Ala Ser Arg Thr Cys 4565 4570 4575 4580 CGG CCG GGC CAG TTT CGGTGT GCT AAT GGC CGC TGC ATC CCG CAG GCC 11059 Arg Pro Gly Gln Phe ArgCys Ala Asn Gly Arg Cys Ile Pro Gln Ala 4585 4590 4595 TGG AAG TGT GATGTG GAT AAT GAT TGT GGA GAC CAC TCG GAT GAG CCC 11107 Trp Lys Cys AspVal Asp Asn Asp Cys Gly Asp His Ser Asp Glu Pro 4600 4605 4610 ATT GAAGAA TGC ATG AGC TCT GCC CAT CTC TGT GAC AAC TTC ACA GAA 11155 Ile GluGlu Cys Met Ser Ser Ala His Leu Cys Asp Asn Phe Thr Glu 4615 4620 4625TTC AGC TGC AAA ACA AAT TAC CGC TGC ATC CCA AAG TGG GCC GTG TGC 11203Phe Ser Cys Lys Thr Asn Tyr Arg Cys Ile Pro Lys Trp Ala Val Cys 46304635 4640 AAT GGT GTA GAT GAC TGC AGG GAC AAC AGT GAT GAG CAA GGC TGTGAG 11251 Asn Gly Val Asp Asp Cys Arg Asp Asn Ser Asp Glu Gln Gly CysGlu 4645 4650 4655 4660 GAG AGG ACA TGC CAT CCT GTG GGG GAT TTC CGC TGTAAA AAT CAC CAC 11299 Glu Arg Thr Cys His Pro Val Gly Asp Phe Arg CysLys Asn His His 4665 4670 4675 TGC ATC CCT CTT CGT TGG CAG TGT GAT GGGCAA AAT GAC TGT GGA GAT 11347 Cys Ile Pro Leu Arg Trp Gln Cys Asp GlyGln Asn Asp Cys Gly Asp 4680 4685 4690 AAC TCA GAT GAG GAA AAC TGT GCTCCC CGG GAG TGC ACA GAG AGC GAG 11395 Asn Ser Asp Glu Glu Asn Cys AlaPro Arg Glu Cys Thr Glu Ser Glu 4695 4700 4705 TTT CGA TGT GTC AAT CAGCAG TGC ATT CCC TCG CGA TGG ATC TGT GAC 11443 Phe Arg Cys Val Asn GlnGln Cys Ile Pro Ser Arg Trp Ile Cys Asp 4710 4715 4720 CAT TAC AAC GACTGT GGG GAC AAC TCA GAT GAA CGG GAC TGT GAG ATG 11491 His Tyr Asn AspCys Gly Asp Asn Ser Asp Glu Arg Asp Cys Glu Met 4725 4730 4735 4740 AGGACC TGC CAT CCT GAA TAT TTT CAG TGT ACA AGT GGA CAT TGT GTA 11539 ArgThr Cys His Pro Glu Tyr Phe Gln Cys Thr Ser Gly His Cys Val 4745 47504755 CAC AGT GAA CTG AAA TGC GAT GGA TCC GCT GAC TGT TTG GAT GCG TCT11587 His Ser Glu Leu Lys Cys Asp Gly Ser Ala Asp Cys Leu Asp Ala Ser4760 4765 4770 GAT GAA GCT GAT TGT CCC ACA CGC TTT CCT GAT GGT GCA TACTGC CAG 11635 Asp Glu Ala Asp Cys Pro Thr Arg Phe Pro Asp Gly Ala TyrCys Gln 4775 4780 4785 GCT ACT ATG TTC GAA TGC AAA AAC CAT GTT TGT ATCCCG CCA TAT TGG 11683 Ala Thr Met Phe Glu Cys Lys Asn His Val Cys IlePro Pro Tyr Trp 4790 4795 4800 AAA TGT GAT GGC GAT GAT GAC TGT GGC GATGGT TCA GAT GAA GAA CTT 11731 Lys Cys Asp Gly Asp Asp Asp Cys Gly AspGly Ser Asp Glu Glu Leu 4805 4810 4815 4820 CAC CTG TGC TTG GAT GTT CCCTGT AAT TCA CCA AAC CGT TTC CGG TGT 11779 His Leu Cys Leu Asp Val ProCys Asn Ser Pro Asn Arg Phe Arg Cys 4825 4830 4835 GAC AAC AAT CGC TGCATT TAT AGT CAT GAG GTG TGC AAT GGT GTG GAT 11827 Asp Asn Asn Arg CysIle Tyr Ser His Glu Val Cys Asn Gly Val Asp 4840 4845 4850 GAC TGT GGAGAT GGA ACT GAT GAG ACA GAG GAG CAC TGT AGA AAA CCG 11875 Asp Cys GlyAsp Gly Thr Asp Glu Thr Glu Glu His Cys Arg Lys Pro 4855 4860 4865 ACCCCT AAA CCT TGT ACA GAA TAT GAA TAT AAG TGT GGC AAT GGG CAT 11923 ThrPro Lys Pro Cys Thr Glu Tyr Glu Tyr Lys Cys Gly Asn Gly His 4870 48754880 TGC ATT CCA CAT GAC AAT GTG TGT GAT GAT GCC GAT GAC TGT GGT GAC11971 Cys Ile Pro His Asp Asn Val Cys Asp Asp Ala Asp Asp Cys Gly Asp4885 4890 4895 4900 TGG TCC GAT GAA CTG GGT TGC AAT AAA GGA AAA GAA AGAACA TGT GCT 12019 Trp Ser Asp Glu Leu Gly Cys Asn Lys Gly Lys Glu ArgThr Cys Ala 4905 4910 4915 GAA AAT ATA TGC GAG CAA AAT TGT ACC CAA TTAAAT GAA GGA GGA TTT 12067 Glu Asn Ile Cys Glu Gln Asn Cys Thr Gln LeuAsn Glu Gly Gly Phe 4920 4925 4930 ATC TGC TCC TGT ACA GCT GGG TTC GAAACC AAT GTT TTT GAC AGA ACC 12115 Ile Cys Ser Cys Thr Ala Gly Phe GluThr Asn Val Phe Asp Arg Thr 4935 4940 4945 TCC TGT CTA GAT ATC AAT GAATGT GAA CAA TTT GGG ACT TGT CCC CAG 12163 Ser Cys Leu Asp Ile Asn GluCys Glu Gln Phe Gly Thr Cys Pro Gln 4950 4955 4960 CAC TGC AGA AAT ACCAAA GGA AGT TAT GAG TGT GTC TGT GCT GAT GGC 12211 His Cys Arg Asn ThrLys Gly Ser Tyr Glu Cys Val Cys Ala Asp Gly 4965 4970 4975 4980 TTC ACGTCT ATG AGT GAC CGC CCT GGA AAA CGA TGT GCA GCT GAG GGT 12259 Phe ThrSer Met Ser Asp Arg Pro Gly Lys Arg Cys Ala Ala Glu Gly 4985 4990 4995AGC TCT CCT TTG TTG CTA CTG CCT GAC AAT GTC CGA ATT CGA AAA TAT 12307Ser Ser Pro Leu Leu Leu Leu Pro Asp Asn Val Arg Ile Arg Lys Tyr 50005005 5010 AAT CTC TCA TCT GAG AGG TTC TCA GAG TAT CTT CAA GAT GAG GAATAT 12355 Asn Leu Ser Ser Glu Arg Phe Ser Glu Tyr Leu Gln Asp Glu GluTyr 5015 5020 5025 ATC CAA GCT GTT GAT TAT GAT TGG GAT CCC AAG GAC ATAGGC CTC AGT 12403 Ile Gln Ala Val Asp Tyr Asp Trp Asp Pro Lys Asp IleGly Leu Ser 5030 5035 5040 GTT GTG TAT TAC ACT GTG CGA GGG GAG GGC TCTAGG TTT GGT GCT ATC 12451 Val Val Tyr Tyr Thr Val Arg Gly Glu Gly SerArg Phe Gly Ala Ile 5045 5050 5055 5060 AAA CGT GCC TAC ATC CCC AAC TTTGAA TCC GGC CGC AAT AAT CTT GTG 12499 Lys Arg Ala Tyr Ile Pro Asn PheGlu Ser Gly Arg Asn Asn Leu Val 5065 5070 5075 CAG GAA GTT GAC CTG AAACTG AAA TAC GTA ATG CAG CCA GAT GGA ATA 12547 Gln Glu Val Asp Leu LysLeu Lys Tyr Val Met Gln Pro Asp Gly Ile 5080 5085 5090 GCA GTG GAC TGGGTT GGA AGG CAT ATT TAC TGG TCA GAT GTC AAG AAT 12595 Ala Val Asp TrpVal Gly Arg His Ile Tyr Trp Ser Asp Val Lys Asn 5095 5100 5105 AAA CGCATT GAG GTG GCT AAA CTT GAT GGA AGG TAC AGA AAG TGG CTG 12643 Lys ArgIle Glu Val Ala Lys Leu Asp Gly Arg Tyr Arg Lys Trp Leu 5110 5115 5120ATT TCC ACT GAC CTG GAC CAA CCA GCT GCT ATT GCT GTG AAT CCC AAA 12691Ile Ser Thr Asp Leu Asp Gln Pro Ala Ala Ile Ala Val Asn Pro Lys 51255130 5135 5140 CTA GGG CTT ATG TTC TGG ACT GAC TGG GGA AAG GAA CCT AAAATC GAG 12739 Leu Gly Leu Met Phe Trp Thr Asp Trp Gly Lys Glu Pro LysIle Glu 5145 5150 5155 TCT GCC TGG ATG AAT GGA GAG GAC CGC AAC ATC CTGGTT TTC GAG GAC 12787 Ser Ala Trp Met Asn Gly Glu Asp Arg Asn Ile LeuVal Phe Glu Asp 5160 5165 5170 CTT GGT TGG CCA ACT GGC CTT TCT ATC GATTAT TTG AAC AAT GAC CGA 12835 Leu Gly Trp Pro Thr Gly Leu Ser Ile AspTyr Leu Asn Asn Asp Arg 5175 5180 5185 ATC TAC TGG AGT GAC TTC AAG GAGGAC GTT ATT GAA ACC ATA AAA TAT 12883 Ile Tyr Trp Ser Asp Phe Lys GluAsp Val Ile Glu Thr Ile Lys Tyr 5190 5195 5200 GAT GGG ACT GAT AGG AGAGTC ATT GCA AAG GAA GCA ATG AAC CCT TAC 12931 Asp Gly Thr Asp Arg ArgVal Ile Ala Lys Glu Ala Met Asn Pro Tyr 5205 5210 5215 5220 AGC CTG GACATC TTT GAA GAC CAG TTA TAC TGG ATA TCT AAG GAA AAG 12979 Ser Leu AspIle Phe Glu Asp Gln Leu Tyr Trp Ile Ser Lys Glu Lys 5225 5230 5235 GGAGAA GTA TGG AAA CAA AAT AAA TTT GGG CAA GGA AAG AAA GAG AAA 13027 GlyGlu Val Trp Lys Gln Asn Lys Phe Gly Gln Gly Lys Lys Glu Lys 5240 52455250 ACG CTG GTA GTG AAC CCT TGG CTC ACT CAA GTT CGA ATC TTT CAT CAA13075 Thr Leu Val Val Asn Pro Trp Leu Thr Gln Val Arg Ile Phe His Gln5255 5260 5265 CTC AGA TAC AAT AAG TCA GTG CCC AAC CTT TGC AAA CAG ATCTGC AGC 13123 Leu Arg Tyr Asn Lys Ser Val Pro Asn Leu Cys Lys Gln IleCys Ser 5270 5275 5280 CAC CTC TGC CTT CTG AGA CCT GGA GGA TAC AGC TGTGCC TGT CCC CAA 13171 His Leu Cys Leu Leu Arg Pro Gly Gly Tyr Ser CysAla Cys Pro Gln 5285 5290 5295 5300 GGC TCC AGC TTT ATA GAG GGG AGC ACCACT GAG TGT GAT GCA GCC ATC 13219 Gly Ser Ser Phe Ile Glu Gly Ser ThrThr Glu Cys Asp Ala Ala Ile 5305 5310 5315 GAA CTG CCT ATC AAC CTG CCCCCC CCA TGC AGG TGC ATG CAC GGA GGA 13267 Glu Leu Pro Ile Asn Leu ProPro Pro Cys Arg Cys Met His Gly Gly 5320 5325 5330 AAT TGC TAT TTT GATGAG ACT GAC CTC CCC AAA TGC AAG TGT CCT AGC 13315 Asn Cys Tyr Phe AspGlu Thr Asp Leu Pro Lys Cys Lys Cys Pro Ser 5335 5340 5345 GGC TAC ACCGGA AAA TAT TGT GAA ATG GCG TTT TCA AAA GGC ATC TCT 13363 Gly Tyr ThrGly Lys Tyr Cys Glu Met Ala Phe Ser Lys Gly Ile Ser 5350 5355 5360 CCAGGA ACA ACC GCA GTA GCT GTG CTG TTG ACA ATC CTC TTG ATC GTC 13411 ProGly Thr Thr Ala Val Ala Val Leu Leu Thr Ile Leu Leu Ile Val 5365 53705375 5380 GTA ATT GGA GCT CTG GCA ATT GCA GGA TTC TTC CAC TAT AGA AGGACC 13459 Val Ile Gly Ala Leu Ala Ile Ala Gly Phe Phe His Tyr Arg ArgThr 5385 5390 5395 GGC TCC CTT TTG CCT GCT CTG CCC AAG CTG CCA AGC TTAAGC AGT CTC 13507 Gly Ser Leu Leu Pro Ala Leu Pro Lys Leu Pro Ser LeuSer Ser Leu 5400 5405 5410 GTC AAG CCC TCT GAA AAT GGG AAT GGG GTG ACCTTC AGA TCA GGG GCA 13555 Val Lys Pro Ser Glu Asn Gly Asn Gly Val ThrPhe Arg Ser Gly Ala 5415 5420 5425 GAT CTT AAC ATG GAT ATT GGA GTG TCTGGT TTT GGA CCT GAG ACT GCT 13603 Asp Leu Asn Met Asp Ile Gly Val SerGly Phe Gly Pro Glu Thr Ala 5430 5435 5440 ATT GAC AGG TCA ATG GCA ATGAGT GAA GAC TTT GTC ATG GAA ATG GGG 13651 Ile Asp Arg Ser Met Ala MetSer Glu Asp Phe Val Met Glu Met Gly 5445 5450 5455 5460 AAG CAG CCC ATAATA TTT GAA AAC CCA ATG TAC TCA GCC AGA GAC AGT 13699 Lys Gln Pro IleIle Phe Glu Asn Pro Met Tyr Ser Ala Arg Asp Ser 5465 5470 5475 GCT GTCAAA GTG GTT CAG CCA ATC CAG GTG ACT GTA TCT GAA AAT GTG 13747 Ala ValLys Val Val Gln Pro Ile Gln Val Thr Val Ser Glu Asn Val 5480 5485 5490GAT AAT AAG AAT TAT GGA AGT CCC ATA AAC CCT TCT GAG ATA GTT CCA 13795Asp Asn Lys Asn Tyr Gly Ser Pro Ile Asn Pro Ser Glu Ile Val Pro 54955500 5505 GAG ACA AAC CCA ACT TCA CCA GCT GCT GAT GGA ACT CAG GTG ACAAAA 13843 Glu Thr Asn Pro Thr Ser Pro Ala Ala Asp Gly Thr Gln Val ThrLys 5510 5515 5520 TGG AAT CTC TTC AAA CGA AAA TCT AAA CAA ACT ACC AACTTT GAA AAT 13891 Trp Asn Leu Phe Lys Arg Lys Ser Lys Gln Thr Thr AsnPhe Glu Asn 5525 5530 5535 5540 CCA ATC TAT GCA CAG ATG GAG AAC GAG CAAAAG GAA AGT GTT GCT GCG 13939 Pro Ile Tyr Ala Gln Met Glu Asn Glu GlnLys Glu Ser Val Ala Ala 5545 5550 5555 ACA CCA CCT CCA TCA CCT TCG CTCCCT GCT AAG CCT AAG CCT CCT TCG 13987 Thr Pro Pro Pro Ser Pro Ser LeuPro Ala Lys Pro Lys Pro Pro Ser 5560 5565 5570 AGA AGA GAC CCA ACT CCAACC TAT TCT GCA ACA GAA GAC ACT TTT AAA 14035 Arg Arg Asp Pro Thr ProThr Tyr Ser Ala Thr Glu Asp Thr Phe Lys 5575 5580 5585 GAC ACC GCA AATCTT GTT AAA GAA GAC TCT GAA GTA TAG GATCAAGAAG 14084 Asp Thr Ala Asn LeuVal Lys Glu Asp Ser Glu Val * 5590 5595 5600 AA 14086 4655 amino acidsamino acid linear protein unknown 84 Met Asp Arg Gly Pro Ala Ala Val AlaCys Thr Leu Leu Leu Ala Leu 1 5 10 15 Val Ala Cys Leu Ala Pro Ala SerGly Gln Glu Cys Asp Ser Ala His 20 25 30 Phe Arg Cys Gly Ser Gly His CysIle Pro Ala Asp Trp Arg Cys Asp 35 40 45 Gly Thr Lys Asp Cys Ser Asp AspAla Asp Glu Ile Gly Cys Ala Val 50 55 60 Val Thr Cys Gln Gln Gly Tyr PheLys Cys Gln Ser Glu Gly Gln Cys 65 70 75 80 Ile Pro Ser Ser Trp Val CysAsp Gln Asp Gln Asp Cys Asp Asp Gly 85 90 95 Ser Asp Glu Arg Gln Asp CysSer Gln Ser Thr Cys Ser Ser His Gln 100 105 110 Ile Thr Cys Ser Asn GlyGln Cys Ile Pro Ser Glu Tyr Arg Cys Asp 115 120 125 His Val Arg Asp CysPro Asp Gly Ala Asp Glu Asn Asp Cys Gln Tyr 130 135 140 Pro Thr Cys GluGln Leu Thr Cys Asp Asn Gly Ala Cys Tyr Asn Thr 145 150 155 160 Ser GlnLys Cys Asp Trp Lys Val Asp Cys Arg Asp Ser Ser Asp Glu 165 170 175 IleAsn Cys Thr Glu Ile Cys Leu His Asn Glu Phe Ser Cys Gly Asn 180 185 190Gly Glu Cys Ile Pro Arg Ala Tyr Val Cys Asp His Asp Asn Asp Cys 195 200205 Gln Asp Gly Ser Asp Glu His Ala Cys Asn Tyr Pro Thr Cys Gly Gly 210215 220 Tyr Gln Phe Thr Cys Pro Ser Gly Arg Cys Ile Tyr Gln Asn Trp Val225 230 235 240 Cys Asp Gly Glu Asp Asp Cys Lys Asp Asn Gly Asp Glu AspGly Cys 245 250 255 Glu Ser Gly Pro His Asp Val His Lys Cys Ser Pro ArgGlu Trp Ser 260 265 270 Cys Pro Glu Ser Gly Arg Cys Ile Ser Ile Tyr LysVal Cys Asp Gly 275 280 285 Ile Leu Asp Cys Pro Gly Arg Glu Asp Glu AsnAsn Thr Ser Thr Gly 290 295 300 Lys Tyr Cys Ser Met Thr Leu Cys Ser AlaLeu Asn Cys Gln Tyr Gln 305 310 315 320 Cys His Glu Thr Pro Tyr Gly GlyAla Cys Phe Cys Pro Pro Gly Tyr 325 330 335 Ile Ile Asn His Asn Asp SerArg Thr Cys Val Glu Phe Asp Asp Cys 340 345 350 Gln Ile Trp Gly Ile CysAsp Gln Lys Cys Glu Ser Arg Pro Gly Arg 355 360 365 His Leu Cys His CysGlu Glu Gly Tyr Ile Leu Glu Arg Gly Gln Tyr 370 375 380 Cys Lys Ala AsnAsp Ser Phe Gly Glu Ala Ser Ile Ile Phe Ser Asn 385 390 395 400 Gly ArgAsp Leu Leu Ile Gly Asp Ile His Gly Arg Ser Phe Arg Ile 405 410 415 LeuVal Glu Ser Gln Asn Arg Gly Val Ala Val Gly Val Ala Phe His 420 425 430Tyr His Leu Gln Arg Val Phe Trp Thr Asp Thr Val Gln Asn Lys Val 435 440445 Phe Ser Val Asp Ile Asn Gly Leu Asn Ile Gln Glu Val Leu Asn Val 450455 460 Ser Val Glu Thr Pro Glu Asn Leu Ala Val Asp Trp Val Asn Asn Lys465 470 475 480 Ile Tyr Leu Val Glu Thr Lys Val Asn Arg Ile Asp Met ValAsn Leu 485 490 495 Asp Gly Ser Tyr Arg Val Thr Leu Ile Thr Glu Asn LeuGly His Pro 500 505 510 Arg Gly Ile Ala Val Asp Pro Thr Val Gly Tyr LeuPhe Phe Ser Asp 515 520 525 Trp Glu Ser Leu Ser Gly Glu Pro Lys Leu GluArg Ala Phe Met Asp 530 535 540 Gly Ser Asn Arg Lys Asp Leu Val Lys ThrLys Leu Gly Trp Pro Ala 545 550 555 560 Gly Val Thr Leu Asp Met Ile SerLys Arg Val Tyr Trp Val Asp Ser 565 570 575 Arg Phe Asp Tyr Ile Glu ThrVal Thr Tyr Asp Gly Ile Gln Arg Lys 580 585 590 Thr Val Val His Gly GlySer Leu Ile Pro His Pro Phe Gly Val Ser 595 600 605 Leu Phe Glu Gly GlnVal Phe Phe Thr Asp Trp Thr Lys Met Ala Val 610 615 620 Leu Lys Ala AsnLys Phe Thr Glu Thr Asn Pro Gln Val Tyr Tyr Gln 625 630 635 640 Ala SerLeu Arg Pro Tyr Gly Val Thr Val Tyr His Ser Leu Arg Gln 645 650 655 ProTyr Ala Thr Asn Pro Cys Lys Asp Asn Asn Gly Gly Cys Glu Gln 660 665 670Val Cys Val Leu Ser His Arg Thr Asp Asn Asp Gly Leu Gly Phe Arg 675 680685 Cys Lys Cys Thr Phe Gly Phe Gln Leu Asp Thr Asp Glu Arg His Cys 690695 700 Ile Ala Val Gln Asn Phe Leu Ile Phe Ser Ser Gln Val Ala Ile Arg705 710 715 720 Gly Ile Pro Phe Thr Leu Ser Thr Gln Glu Asp Val Met ValPro Val 725 730 735 Ser Gly Asn Pro Ser Phe Phe Val Gly Ile Asp Phe AspAla Gln Asp 740 745 750 Ser Thr Ile Phe Phe Ser Asp Met Ser Lys His MetIle Phe Lys Gln 755 760 765 Lys Ile Asp Gly Thr Gly Arg Glu Ile Leu AlaAla Asn Arg Val Glu 770 775 780 Asn Val Glu Ser Leu Ala Phe Asp Trp IleSer Lys Asn Leu Tyr Trp 785 790 795 800 Thr Asp Ser His Tyr Lys Ser IleSer Val Met Arg Leu Ala Asp Lys 805 810 815 Thr Arg Arg Thr Val Val GlnTyr Leu Asn Asn Pro Arg Ser Val Val 820 825 830 Val His Pro Phe Ala GlyTyr Leu Phe Phe Thr Asp Trp Phe Arg Pro 835 840 845 Ala Lys Ile Met ArgAla Trp Ser Asp Gly Ser His Leu Leu Pro Val 850 855 860 Ile Asn Thr ThrLeu Gly Trp Pro Asn Gly Leu Ala Ile Asp Trp Ala 865 870 875 880 Ala SerArg Leu Tyr Trp Val Asp Ala Tyr Phe Asp Lys Ile Glu His 885 890 895 SerThr Phe Asp Gly Leu Asp Arg Arg Arg Leu Gly His Ile Glu Gln 900 905 910Met Thr His Pro Phe Gly Leu Ala Ile Phe Gly Glu His Leu Phe Phe 915 920925 Thr Asp Trp Arg Leu Gly Ala Ile Ile Arg Val Arg Lys Ala Asp Gly 930935 940 Gly Glu Met Thr Val Ile Arg Ser Gly Ile Ala Tyr Ile Leu His Leu945 950 955 960 Lys Ser Tyr Asp Val Asn Ile Gln Thr Gly Ser Asn Ala CysAsn Gln 965 970 975 Pro Thr His Pro Asn Gly Asp Cys Ser His Phe Cys PhePro Val Pro 980 985 990 Asn Phe Gln Arg Val Cys Gly Cys Pro Tyr Gly MetArg Leu Ala Ser 995 1000 1005 Asn His Leu Thr Cys Glu Gly Asp Pro ThrAsn Glu Pro Pro Thr Glu 1010 1015 1020 Gln Cys Gly Leu Phe Ser Phe ProCys Lys Asn Gly Arg Cys Val Pro 1025 1030 1035 1040 Asn Tyr Tyr Leu CysAsp Gly Val Asp Asp Cys His Asp Asn Ser Asp 1045 1050 1055 Glu Gln LeuCys Gly Thr Leu Asn Asn Thr Cys Ser Ser Ser Ala Phe 1060 1065 1070 ThrCys Gly His Gly Glu Cys Ile Pro Ala His Trp Arg Cys Asp Lys 1075 10801085 Arg Asn Asp Cys Val Asp Gly Ser Asp Glu His Asn Cys Pro Thr His1090 1095 1100 Ala Pro Ala Ser Cys Leu Asp Thr Gln Tyr Thr Cys Asp AsnHis Gln 1105 1110 1115 1120 Cys Ile Ser Lys Asn Trp Val Cys Asp Thr AspAsn Asp Cys Gly Asp 1125 1130 1135 Gly Ser Asp Glu Lys Asn Cys Asn SerThr Glu Thr Cys Gln Pro Ser 1140 1145 1150 Gln Phe Asn Cys Pro Asn HisArg Cys Ile Asp Leu Ser Phe Val Cys 1155 1160 1165 Asp Gly Asp Lys AspCys Val Asp Gly Ser Asp Glu Val Gly Cys Val 1170 1175 1180 Leu Asn CysThr Ala Ser Gln Phe Lys Cys Ala Ser Gly Asp Lys Cys 1185 1190 1195 1200Ile Gly Val Thr Asn Arg Cys Asp Gly Val Phe Asp Cys Ser Asp Asn 12051210 1215 Ser Asp Glu Ala Gly Cys Pro Thr Arg Pro Pro Gly Met Cys HisSer 1220 1225 1230 Asp Glu Phe Gln Cys Gln Glu Asp Gly Ile Cys Ile ProAsn Phe Trp 1235 1240 1245 Glu Cys Asp Gly His Pro Asp Cys Leu Tyr GlySer Asp Glu His Asn 1250 1255 1260 Ala Cys Val Pro Lys Thr Cys Pro SerSer Tyr Phe His Cys Asp Asn 1265 1270 1275 1280 Gly Asn Cys Ile His ArgAla Trp Leu Cys Asp Arg Asp Asn Asp Cys 1285 1290 1295 Gly Asp Met SerAsp Glu Lys Asp Cys Pro Thr Gln Pro Phe Arg Cys 1300 1305 1310 Pro SerTrp Gln Trp Gln Cys Leu Gly His Asn Ile Cys Val Asn Leu 1315 1320 1325Ser Val Val Cys Asp Gly Ile Phe Asp Cys Pro Asn Gly Thr Asp Glu 13301335 1340 Ser Pro Leu Cys Asn Gly Asn Ser Cys Ser Asp Phe Asn Gly GlyCys 1345 1350 1355 1360 Thr His Glu Cys Val Gln Glu Pro Phe Gly Ala LysCys Leu Cys Pro 1365 1370 1375 Leu Gly Phe Leu Leu Ala Asn Asp Ser LysThr Cys Glu Asp Ile Asp 1380 1385 1390 Glu Cys Asp Ile Leu Gly Ser CysSer Gln His Cys Tyr Asn Met Arg 1395 1400 1405 Gly Ser Phe Arg Cys SerCys Asp Thr Gly Tyr Met Leu Glu Ser Asp 1410 1415 1420 Gly Arg Thr CysLys Val Thr Ala Ser Glu Ser Leu Leu Leu Leu Val 1425 1430 1435 1440 AlaSer Gln Asn Lys Ile Ile Ala Asp Ser Val Thr Ser Gln Val His 1445 14501455 Asn Ile Tyr Ser Leu Val Glu Asn Gly Ser Tyr Ile Val Ala Val Asp1460 1465 1470 Phe Asp Ser Ile Ser Gly Arg Ile Phe Trp Ser Asp Ala ThrGln Gly 1475 1480 1485 Lys Thr Trp Ser Ala Phe Gln Asn Gly Thr Asp ArgArg Val Val Phe 1490 1495 1500 Asp Ser Ser Ile Ile Leu Thr Glu Thr IleAla Ile Asp Trp Val Gly 1505 1510 1515 1520 Arg Asn Leu Tyr Trp Thr AspTyr Ala Leu Glu Thr Ile Glu Val Ser 1525 1530 1535 Lys Ile Asp Gly SerHis Arg Thr Val Leu Ile Ser Lys Asn Leu Thr 1540 1545 1550 Asn Pro ArgGly Leu Ala Leu Asp Pro Arg Met Asn Glu His Leu Leu 1555 1560 1565 PheTrp Ser Asp Trp Gly His His Pro Arg Ile Glu Arg Ala Ser Met 1570 15751580 Asp Gly Ser Met Arg Thr Val Ile Val Gln Asp Lys Ile Phe Trp Pro1585 1590 1595 1600 Cys Gly Leu Thr Ile Asp Tyr Pro Asn Arg Leu Leu TyrPhe Met Asp 1605 1610 1615 Ser Tyr Leu Asp Tyr Met Asp Phe Cys Asp TyrAsn Gly His His Arg 1620 1625 1630 Arg Gln Val Ile Ala Ser Asp Leu IleIle Arg His Pro Tyr Ala Leu 1635 1640 1645 Thr Leu Phe Glu Asp Ser ValTyr Trp Thr Asp Arg Ala Thr Arg Arg 1650 1655 1660 Val Met Arg Ala AsnLys Trp His Gly Gly Asn Gln Ser Val Val Met 1665 1670 1675 1680 Tyr AsnIle Gln Trp Pro Leu Gly Ile Val Ala Val His Pro Ser Lys 1685 1690 1695Gln Pro Asn Ser Val Asn Pro Cys Ala Phe Ser Arg Cys Ser His Leu 17001705 1710 Cys Leu Leu Ser Ser Gln Gly Pro His Phe Tyr Ser Cys Val CysPro 1715 1720 1725 Ser Gly Trp Ser Leu Ser Pro Asp Leu Leu Asn Cys LeuArg Asp Asp 1730 1735 1740 Gln Pro Phe Leu Ile Thr Val Arg Gln His IleIle Phe Gly Ile Ser 1745 1750 1755 1760 Leu Asn Pro Glu Val Lys Ser AsnAsp Ala Met Val Pro Ile Ala Gly 1765 1770 1775 Ile Gln Asn Gly Leu AspVal Glu Phe Asp Asp Ala Glu Gln Tyr Ile 1780 1785 1790 Tyr Trp Val GluAsn Pro Gly Glu Ile His Arg Val Lys Thr Asp Gly 1795 1800 1805 Thr AsnArg Thr Val Phe Ala Ser Ile Ser Met Val Gly Pro Ser Met 1810 1815 1820Asn Leu Ala Leu Asp Trp Ile Ser Arg Asn Leu Tyr Ser Thr Asn Pro 18251830 1835 1840 Arg Thr Gln Ser Ile Glu Val Leu Thr Leu His Gly Asp IleArg Tyr 1845 1850 1855 Arg Lys Thr Leu Ile Ala Asn Asp Gly Thr Ala LeuGly Val Gly Phe 1860 1865 1870 Pro Ile Gly Ile Thr Val Asp Pro Ala ArgGly Lys Leu Tyr Trp Ser 1875 1880 1885 Asp Gln Gly Thr Asp Ser Gly ValPro Ala Lys Ile Ala Ser Ala Asn 1890 1895 1900 Met Asp Gly Thr Ser ValLys Thr Leu Phe Thr Gly Asn Leu Glu His 1905 1910 1915 1920 Leu Glu CysVal Thr Leu Asp Ile Glu Glu Gln Lys Leu Tyr Trp Ala 1925 1930 1935 ValThr Gly Arg Gly Val Ile Glu Arg Gly Asn Val Asp Gly Thr Asp 1940 19451950 Arg Met Ile Leu Val His Gln Leu Ser His Pro Trp Gly Ile Ala Val1955 1960 1965 His Asp Ser Phe Leu Tyr Tyr Thr Asp Glu Gln Tyr Glu ValIle Glu 1970 1975 1980 Arg Val Asp Lys Ala Thr Gly Ala Asn Lys Ile ValLeu Arg Asp Asn 1985 1990 1995 2000 Val Pro Asn Leu Arg Gly Leu Gln ValTyr His Arg Arg Asn Ala Ala 2005 2010 2015 Glu Ser Ser Asn Gly Cys SerAsn Asn Met Asn Ala Cys Gln Gln Ile 2020 2025 2030 Cys Leu Pro Val ProGly Gly Leu Phe Ser Cys Ala Cys Ala Thr Gly 2035 2040 2045 Phe Lys LeuAsn Pro Asp Asn Arg Ser Cys Ser Pro Tyr Asn Ser Phe 2050 2055 2060 IleVal Val Ser Met Leu Ser Ala Ile Arg Gly Phe Ser Leu Glu Leu 2065 20702075 2080 Ser Asp His Ser Glu Thr Met Val Pro Val Ala Gly Gln Gly ArgAsn 2085 2090 2095 Ala Leu His Val Asp Val Asp Val Ser Ser Gly Phe IleTyr Trp Cys 2100 2105 2110 Asp Phe Ser Ser Ser Val Ala Ser Asp Asn AlaIle Arg Arg Ile Lys 2115 2120 2125 Pro Asp Gly Ser Ser Leu Met Asn IleVal Thr His Gly Ile Gly Glu 2130 2135 2140 Asn Gly Val Arg Gly Ile AlaVal Asp Trp Val Ala Gly Asn Leu Tyr 2145 2150 2155 2160 Phe Thr Asn AlaPhe Val Ser Glu Thr Leu Ile Glu Val Leu Arg Ile 2165 2170 2175 Asn ThrThr Tyr Arg Arg Val Leu Leu Lys Val Thr Val Asp Met Pro 2180 2185 2190Arg His Ile Val Val Asp Pro Lys Asn Arg Tyr Leu Phe Trp Ala Asp 21952200 2205 Tyr Gly Gln Arg Pro Lys Ile Glu Arg Ser Phe Leu Asp Cys ThrAsn 2210 2215 2220 Arg Thr Val Leu Val Ser Glu Gly Ile Val Thr Pro ArgGly Leu Ala 2225 2230 2235 2240 Val Asp Arg Ser Asp Gly Tyr Val Tyr TrpVal Asp Asp Ser Leu Asp 2245 2250 2255 Ile Ile Ala Arg Ile Arg Ile AsnGly Glu Asn Ser Glu Val Ile Arg 2260 2265 2270 Tyr Gly Ser Arg Tyr ProThr Pro Tyr Gly Ile Thr Val Phe Glu Asn 2275 2280 2285 Ser Ile Ile TrpVal Asp Arg Asn Leu Lys Lys Ile Phe Gln Ala Ser 2290 2295 2300 Lys GluPro Glu Asn Thr Glu Pro Pro Thr Val Ile Arg Asp Asn Ile 2305 2310 23152320 Asn Trp Leu Arg Asp Val Thr Ile Phe Asp Lys Gln Val Gln Pro Arg2325 2330 2335 Ser Pro Ala Glu Val Asn Asn Asn Pro Cys Leu Glu Asn AsnGly Gly 2340 2345 2350 Cys Ser His Leu Cys Phe Ala Leu Pro Gly Leu HisThr Pro Lys Cys 2355 2360 2365 Asp Cys Ala Phe Gly Thr Leu Gln Ser AspGly Lys Asn Cys Ala Ile 2370 2375 2380 Ser Thr Glu Asn Phe Leu Ile PheAla Leu Ser Asn Ser Leu Arg Ser 2385 2390 2395 2400 Leu His Leu Asp ProGlu Asn His Ser Pro Pro Phe Gln Thr Ile Asn 2405 2410 2415 Val Glu ArgThr Val Met Ser Leu Asp Tyr Asp Ser Val Ser Asp Arg 2420 2425 2430 IleTyr Phe Thr Gln Asn Leu Ala Ser Gly Val Gly Gln Ile Ser Tyr 2435 24402445 Ala Thr Leu Ser Ser Gly Ile His Thr Pro Thr Val Ile Ala Ser Gly2450 2455 2460 Ile Gly Thr Ala Asp Gly Ile Ala Phe Asp Trp Ile Thr ArgArg Ile 2465 2470 2475 2480 Tyr Tyr Ser Asp Tyr Leu Asn Gln Met Ile AsnSer Met Ala Glu Asp 2485 2490 2495 Gly Ser Asn Arg Thr Val Ile Ala ArgVal Pro Lys Pro Arg Ala Ile 2500 2505 2510 Val Leu Asp Pro Cys Gln GlyTyr Leu Tyr Trp Ala Asp Trp Asp Thr 2515 2520 2525 His Ala Lys Ile GluArg Ala Thr Leu Gly Gly Asn Phe Arg Val Pro 2530 2535 2540 Ile Val AsnSer Ser Leu Val Met Pro Ser Gly Leu Thr Leu Asp Tyr 2545 2550 2555 2560Glu Glu Asp Leu Leu Tyr Trp Val Asp Ala Ser Leu Gln Arg Ile Glu 25652570 2575 Arg Ser Thr Leu Thr Gly Val Asp Arg Glu Val Ile Val Asn AlaAla 2580 2585 2590 Val His Ala Phe Gly Leu Thr Leu Tyr Gly Gln Tyr IleTyr Trp Thr 2595 2600 2605 Asp Leu Tyr Thr Gln Arg Ile Tyr Arg Ala AsnLys Tyr Asp Gly Ser 2610 2615 2620 Gly Gln Ile Ala Met Thr Thr Asn LeuLeu Ser Gln Pro Arg Gly Ile 2625 2630 2635 2640 Asn Thr Val Val Lys AsnGln Lys Gln Gln Cys Asn Asn Pro Cys Glu 2645 2650 2655 Gln Phe Asn GlyGly Cys Ser His Ile Cys Ala Pro Gly Pro Asn Gly 2660 2665 2670 Ala GluCys Gln Cys Pro His Glu Gly Asn Trp Tyr Leu Ala Asn Asn 2675 2680 2685Arg Lys His Cys Ile Val Asp Asn Gly Glu Arg Cys Gly Ala Ser Ser 26902695 2700 Phe Thr Cys Ser Asn Gly Arg Cys Ile Ser Glu Glu Trp Lys CysAsp 2705 2710 2715 2720 Asn Asp Asn Asp Cys Gly Asp Gly Ser Asp Glu MetGlu Ser Val Cys 2725 2730 2735 Ala Leu His Thr Cys Ser Pro Thr Ala PheThr Cys Ala Asn Gly Arg 2740 2745 2750 Cys Val Gln Tyr Ser Tyr Arg CysAsp Tyr Tyr Asn Asp Cys Gly Asp 2755 2760 2765 Gly Ser Asp Glu Ala GlyCys Leu Phe Arg Asp Cys Asn Ala Thr Thr 2770 2775 2780 Glu Phe Met CysAsn Asn Arg Arg Cys Ile Pro Arg Glu Phe Ile Cys 2785 2790 2795 2800 AsnGly Val Asp Asn Cys His Asp Asn Asn Thr Ser Asp Glu Lys Asn 2805 28102815 Cys Pro Asp Arg Thr Cys Gln Ser Gly Tyr Thr Lys Cys His Asn Ser2820 2825 2830 Asn Ile Cys Ile Pro Arg Val Tyr Leu Cys Asp Gly Asp AsnAsp Cys 2835 2840 2845 Gly Asp Asn Ser Asp Glu Asn Pro Thr Tyr Cys ThrThr His Thr Cys 2850 2855 2860 Ser Ser Ser Glu Phe Gln Cys Ala Ser GlyArg Cys Ile Pro Gln His 2865 2870 2875 2880 Trp Tyr Cys Asp Gln Glu ThrAsp Cys Phe Asp Ala Ser Asp Glu Pro 2885 2890 2895 Ala Ser Cys Gly HisSer Glu Arg Thr Cys Leu Ala Asp Glu Phe Lys 2900 2905 2910 Cys Asp GlyGly Arg Cys Ile Pro Ser Glu Trp Ile Cys Asp Gly Asp 2915 2920 2925 AsnAsp Cys Gly Asp Met Ser Asp Glu Asp Lys Arg His Gln Cys Gln 2930 29352940 Asn Gln Asn Cys Ser Asp Ser Glu Phe Leu Cys Val Asn Asp Arg Pro2945 2950 2955 2960 Pro Asp Arg Arg Cys Ile Pro Gln Ser Trp Val Cys AspGly Asp Val 2965 2970 2975 Asp Cys Thr Asp Gly Tyr Asp Glu Asn Gln AsnCys Thr Arg Arg Thr 2980 2985 2990 Cys Ser Glu Asn Glu Phe Thr Cys GlyTyr Gly Leu Cys Ile Pro Lys 2995 3000 3005 Ile Phe Arg Cys Asp Arg HisAsn Asp Cys Gly Asp Tyr Ser Asp Glu 3010 3015 3020 Arg Gly Cys Leu TyrGln Thr Cys Gln Gln Asn Gln Phe Thr Cys Gln 3025 3030 3035 3040 Asn GlyArg Cys Ile Ser Lys Thr Phe Val Cys Asp Glu Asp Asn Asp 3045 3050 3055Cys Gly Asp Gly Ser Asp Glu Leu Met His Leu Cys His Thr Pro Glu 30603065 3070 Pro Thr Cys Pro Pro His Glu Phe Lys Cys Asp Asn Gly Arg CysIle 3075 3080 3085 Glu Met Met Lys Leu Cys Asn His Leu Asp Asp Cys LeuAsp Asn Ser 3090 3095 3100 Asp Glu Lys Gly Cys Gly Ile Asn Glu Cys HisAsp Pro Ser Ile Ser 3105 3110 3115 3120 Gly Cys Asp His Asn Cys Thr AspThr Leu Thr Ser Phe Tyr Cys Ser 3125 3130 3135 Cys Arg Pro Gly Tyr LysLeu Met Ser Asp Lys Arg Thr Cys Val Asp 3140 3145 3150 Ile Asp Glu CysThr Glu Met Pro Phe Val Cys Ser Gln Lys Cys Glu 3155 3160 3165 Asn ValIle Gly Ser Tyr Ile Cys Lys Cys Ala Pro Gly Tyr Leu Arg 3170 3175 3180Glu Pro Asp Gly Lys Thr Cys Arg Gln Asn Ser Asn Ile Glu Pro Tyr 31853190 3195 3200 Leu Ile Phe Ser Asn Arg Tyr Tyr Leu Arg Asn Leu Thr IleAsp Gly 3205 3210 3215 Tyr Phe Tyr Ser Leu Ile Leu Glu Gly Leu Asp AsnVal Val Ala Leu 3220 3225 3230 Asp Phe Asp Arg Val Glu Lys Arg Leu TyrTrp Ile Asp Thr Gln Arg 3235 3240 3245 Gln Val Ile Glu Arg Met Phe LeuAsn Lys Thr Asn Lys Glu Thr Ile 3250 3255 3260 Ile Asn His Arg Leu ProAla Ala Glu Ser Leu Ala Val Asp Trp Val 3265 3270 3275 3280 Ser Arg LysLeu Tyr Trp Leu Asp Ala Arg Leu Asp Gly Leu Phe Val 3285 3290 3295 SerAsp Leu Asn Gly Gly His Arg Arg Met Leu Ala Gln His Cys Val 3300 33053310 Asp Ala Asn Asn Thr Phe Cys Phe Asp Asn Pro Arg Gly Leu Ala Leu3315 3320 3325 His Pro Gln Tyr Gly Tyr Leu Tyr Trp Ala Asp Trp Gly HisArg Ala 3330 3335 3340 Tyr Ile Gly Arg Val Gly Met Asp Gly Thr Asn LysSer Val Ile Ile 3345 3350 3355 3360 Ser Thr Lys Leu Glu Trp Pro Asn GlyIle Thr Ile Asp Tyr Thr Asn 3365 3370 3375 Asp Leu Leu Tyr Trp Ala AspAla His Leu Gly Tyr Ile Glu Tyr Ser 3380 3385 3390 Asp Leu Glu Gly HisHis Arg His Thr Val Tyr Asp Gly Ala Leu Pro 3395 3400 3405 His Pro PheAla Ile Thr Ile Phe Glu Asp Thr Ile Tyr Trp Thr Asp 3410 3415 3420 TrpAsn Thr Arg Thr Val Glu Lys Gly Asn Lys Tyr Asp Gly Ser Asn 3425 34303435 3440 Arg Gln Thr Leu Val Asn Thr Thr His Arg Pro Phe Asp Ile HisVal 3445 3450 3455 Tyr His Pro Tyr Arg Gln Pro Ile Val Ser Asn Pro CysGly Thr Asn 3460 3465 3470 Asn Gly Gly Cys Ser His Leu Cys Leu Ile LysPro Gly Gly Lys Gly 3475 3480 3485 Phe Thr Cys Glu Cys Pro Asp Asp PheArg Thr Leu Gln Leu Ser Gly 3490 3495 3500 Ser Thr Tyr Cys Met Pro MetCys Ser Ser Thr Gln Phe Leu Cys Ala 3505 3510 3515 3520 Asn Asn Glu LysCys Ile Pro Ile Trp Trp Lys Cys Asp Gly Gln Lys 3525 3530 3535 Asp CysSer Asp Gly Ser Asp Glu Leu Ala Leu Cys Pro Gln Arg Phe 3540 3545 3550Cys Arg Leu Gly Gln Phe Gln Cys Ser Asp Gly Asn Cys Thr Ser Pro 35553560 3565 Gln Thr Leu Cys Asn Ala His Gln Asn Cys Pro Asp Gly Ser AspGlu 3570 3575 3580 Asp Arg Leu Leu Cys Glu Asn His His Cys Asp Ser AsnGlu Trp Gln 3585 3590 3595 3600 Cys Ala Asn Lys Arg Cys Ile Pro Glu SerTrp Gln Cys Asp Thr Phe 3605 3610 3615 Asn Asp Cys Glu Asp Asn Ser AspGlu Asp Ser Ser His Cys Ala Ser 3620 3625 3630 Arg Thr Cys Arg Pro GlyGln Phe Arg Cys Ala Asn Gly Arg Cys Ile 3635 3640 3645 Pro Gln Ala TrpLys Cys Asp Val Asp Asn Asp Cys Gly Asp His Ser 3650 3655 3660 Asp GluPro Ile Glu Glu Cys Met Ser Ser Ala His Leu Cys Asp Asn 3665 3670 36753680 Phe Thr Glu Phe Ser Cys Lys Thr Asn Tyr Arg Cys Ile Pro Lys Trp3685 3690 3695 Ala Val Cys Asn Gly Val Asp Asp Cys Arg Asp Asn Ser AspGlu Gln 3700 3705 3710 Gly Cys Glu Glu Arg Thr Cys His Pro Val Gly AspPhe Arg Cys Lys 3715 3720 3725 Asn His His Cys Ile Pro Leu Arg Trp GlnCys Asp Gly Gln Asn Asp 3730 3735 3740 Cys Gly Asp Asn Ser Asp Glu GluAsn Cys Ala Pro Arg Glu Cys Thr 3745 3750 3755 3760 Glu Ser Glu Phe ArgCys Val Asn Gln Gln Cys Ile Pro Ser Arg Trp 3765 3770 3775 Ile Cys AspHis Tyr Asn Asp Cys Gly Asp Asn Ser Asp Glu Arg Asp 3780 3785 3790 CysGlu Met Arg Thr Cys His Pro Glu Tyr Phe Gln Cys Thr Ser Gly 3795 38003805 His Cys Val His Ser Glu Leu Lys Cys Asp Gly Ser Ala Asp Cys Leu3810 3815 3820 Asp Ala Ser Asp Glu Ala Asp Cys Pro Thr Arg Phe Pro AspGly Ala 3825 3830 3835 3840 Tyr Cys Gln Ala Thr Met Phe Glu Cys Lys AsnHis Val Cys Ile Pro 3845 3850 3855 Pro Tyr Trp Lys Cys Asp Gly Asp AspAsp Cys Gly Asp Gly Ser Asp 3860 3865 3870 Glu Glu Leu His Leu Cys LeuAsp Val Pro Cys Asn Ser Pro Asn Arg 3875 3880 3885 Phe Arg Cys Asp AsnAsn Arg Cys Ile Tyr Ser His Glu Val Cys Asn 3890 3895 3900 Gly Val AspAsp Cys Gly Asp Gly Thr Asp Glu Thr Glu Glu His Cys 3905 3910 3915 3920Arg Lys Pro Thr Pro Lys Pro Cys Thr Glu Tyr Glu Tyr Lys Cys Gly 39253930 3935 Asn Gly His Cys Ile Pro His Asp Asn Val Cys Asp Asp Ala AspAsp 3940 3945 3950 Cys Gly Asp Trp Ser Asp Glu Leu Gly Cys Asn Lys GlyLys Glu Arg 3955 3960 3965 Thr Cys Ala Glu Asn Ile Cys Glu Gln Asn CysThr Gln Leu Asn Glu 3970 3975 3980 Gly Gly Phe Ile Cys Ser Cys Thr AlaGly Phe Glu Thr Asn Val Phe 3985 3990 3995 4000 Asp Arg Thr Ser Cys LeuAsp Ile Asn Glu Cys Glu Gln Phe Gly Thr 4005 4010 4015 Cys Pro Gln HisCys Arg Asn Thr Lys Gly Ser Tyr Glu Cys Val Cys 4020 4025 4030 Ala AspGly Phe Thr Ser Met Ser Asp Arg Pro Gly Lys Arg Cys Ala 4035 4040 4045Ala Glu Gly Ser Ser Pro Leu Leu Leu Leu Pro Asp Asn Val Arg Ile 40504055 4060 Arg Lys Tyr Asn Leu Ser Ser Glu Arg Phe Ser Glu Tyr Leu GlnAsp 4065 4070 4075 4080 Glu Glu Tyr Ile Gln Ala Val Asp Tyr Asp Trp AspPro Lys Asp Ile 4085 4090 4095 Gly Leu Ser Val Val Tyr Tyr Thr Val ArgGly Glu Gly Ser Arg Phe 4100 4105 4110 Gly Ala Ile Lys Arg Ala Tyr IlePro Asn Phe Glu Ser Gly Arg Asn 4115 4120 4125 Asn Leu Val Gln Glu ValAsp Leu Lys Leu Lys Tyr Val Met Gln Pro 4130 4135 4140 Asp Gly Ile AlaVal Asp Trp Val Gly Arg His Ile Tyr Trp Ser Asp 4145 4150 4155 4160 ValLys Asn Lys Arg Ile Glu Val Ala Lys Leu Asp Gly Arg Tyr Arg 4165 41704175 Lys Trp Leu Ile Ser Thr Asp Leu Asp Gln Pro Ala Ala Ile Ala Val4180 4185 4190 Asn Pro Lys Leu Gly Leu Met Phe Trp Thr Asp Trp Gly LysGlu Pro 4195 4200 4205 Lys Ile Glu Ser Ala Trp Met Asn Gly Glu Asp ArgAsn Ile Leu Val 4210 4215 4220 Phe Glu Asp Leu Gly Trp Pro Thr Gly LeuSer Ile Asp Tyr Leu Asn 4225 4230 4235 4240 Asn Asp Arg Ile Tyr Trp SerAsp Phe Lys Glu Asp Val Ile Glu Thr 4245 4250 4255 Ile Lys Tyr Asp GlyThr Asp Arg Arg Val Ile Ala Lys Glu Ala Met 4260 4265 4270 Asn Pro TyrSer Leu Asp Ile Phe Glu Asp Gln Leu Tyr Trp Ile Ser 4275 4280 4285 LysGlu Lys Gly Glu Val Trp Lys Gln Asn Lys Phe Gly Gln Gly Lys 4290 42954300 Lys Glu Lys Thr Leu Val Val Asn Pro Trp Leu Thr Gln Val Arg Ile4305 4310 4315 4320 Phe His Gln Leu Arg Tyr Asn Lys Ser Val Pro Asn LeuCys Lys Gln 4325 4330 4335 Ile Cys Ser His Leu Cys Leu Leu Arg Pro GlyGly Tyr Ser Cys Ala 4340 4345 4350 Cys Pro Gln Gly Ser Ser Phe Ile GluGly Ser Thr Thr Glu Cys Asp 4355 4360 4365 Ala Ala Ile Glu Leu Pro IleAsn Leu Pro Pro Pro Cys Arg Cys Met 4370 4375 4380 His Gly Gly Asn CysTyr Phe Asp Glu Thr Asp Leu Pro Lys Cys Lys 4385 4390 4395 4400 Cys ProSer Gly Tyr Thr Gly Lys Tyr Cys Glu Met Ala Phe Ser Lys 4405 4410 4415Gly Ile Ser Pro Gly Thr Thr Ala Val Ala Val Leu Leu Thr Ile Leu 44204425 4430 Leu Ile Val Val Ile Gly Ala Leu Ala Ile Ala Gly Phe Phe HisTyr 4435 4440 4445 Arg Arg Thr Gly Ser Leu Leu Pro Ala Leu Pro Lys LeuPro Ser Leu 4450 4455 4460 Ser Ser Leu Val Lys Pro Ser Glu Asn Gly AsnGly Val Thr Phe Arg 4465 4470 4475 4480 Ser Gly Ala Asp Leu Asn Met AspIle Gly Val Ser Gly Phe Gly Pro 4485 4490 4495 Glu Thr Ala Ile Asp ArgSer Met Ala Met Ser Glu Asp Phe Val Met 4500 4505 4510 Glu Met Gly LysGln Pro Ile Ile Phe Glu Asn Pro Met Tyr Ser Ala 4515 4520 4525 Arg AspSer Ala Val Lys Val Val Gln Pro Ile Gln Val Thr Val Ser 4530 4535 4540Glu Asn Val Asp Asn Lys Asn Tyr Gly Ser Pro Ile Asn Pro Ser Glu 45454550 4555 4560 Ile Val Pro Glu Thr Asn Pro Thr Ser Pro Ala Ala Asp GlyThr Gln 4565 4570 4575 Val Thr Lys Trp Asn Leu Phe Lys Arg Lys Ser LysGln Thr Thr Asn 4580 4585 4590 Phe Glu Asn Pro Ile Tyr Ala Gln Met GluAsn Glu Gln Lys Glu Ser 4595 4600 4605 Val Ala Ala Thr Pro Pro Pro SerPro Ser Leu Pro Ala Lys Pro Lys 4610 4615 4620 Pro Pro Ser Arg Arg AspPro Thr Pro Thr Tyr Ser Ala Thr Glu Asp 4625 4630 4635 4640 Thr Phe LysAsp Thr Ala Asn Leu Val Lys Glu Asp Ser Glu Val 4645 4650 4655 14042base pairs nucleic acid single linear cDNA NO NO Homo sapiens PlacentaCDS 68..14035 85 CGGTGCGGTG TGCTACGCGC GCCCACCTCC CGGGGAAGGA ACGGCGAGGCCGGGGACCGT 60 CGCGGAG ATG GAT CGC GGG CCG GCA GCA GTG GCG TGC ACG CTGCTC CTG 109 Met Asp Arg Gly Pro Ala Ala Val Ala Cys Thr Leu Leu Leu 1 510 GCT CTC GTC GCC TGC CTA GCC CCG GCC AGT GGC CAA GAA TGT GAC AGT 157Ala Leu Val Ala Cys Leu Ala Pro Ala Ser Gly Gln Glu Cys Asp Ser 15 20 2530 GCG CAT TTT CGC TGT GGA AGT GGG CAT TGC ATC CCT GCA GAC TGG AGG 205Ala His Phe Arg Cys Gly Ser Gly His Cys Ile Pro Ala Asp Trp Arg 35 40 45TGT GAT GGG ACC AAA GAC TGT TCA GAT GAC GCG GAT GAA ATT GGC TGC 253 CysAsp Gly Thr Lys Asp Cys Ser Asp Asp Ala Asp Glu Ile Gly Cys 50 55 60 GCTGTT GTG ACC TGC CAG CAG GGC TAT TTC AAG TGC CAG AGT GAG GGA 301 Ala ValVal Thr Cys Gln Gln Gly Tyr Phe Lys Cys Gln Ser Glu Gly 65 70 75 CAA TGCATC CCC AGC TCC TGG GTG TGT GAC CAA GAT CAA GAC TGT GAT 349 Gln Cys IlePro Ser Ser Trp Val Cys Asp Gln Asp Gln Asp Cys Asp 80 85 90 GAT GGC TCAGAT GAA CGT CAA GAT TGC TCA CAA AGT ACA TGC TCA AGT 397 Asp Gly Ser AspGlu Arg Gln Asp Cys Ser Gln Ser Thr Cys Ser Ser 95 100 105 110 CAT CAGATA ACA TGC TCC AAT GGT CAG TGT ATC CCA AGT GAA TAC AGG 445 His Gln IleThr Cys Ser Asn Gly Gln Cys Ile Pro Ser Glu Tyr Arg 115 120 125 TGC GACCAC GTC AGA GAC TGC CCC GAT GGA GCT GAT GAG AAT GAC TGC 493 Cys Asp HisVal Arg Asp Cys Pro Asp Gly Ala Asp Glu Asn Asp Cys 130 135 140 CAG TACCCA ACA TGT GAG CAG CTT ACT TGT GAC AAT GGG GCC TGC TAT 541 Gln Tyr ProThr Cys Glu Gln Leu Thr Cys Asp Asn Gly Ala Cys Tyr 145 150 155 AAC ACCAGT CAG AAG TGT GAT TGG AAA GTT GAT TGC AGG GAC TCC TCA 589 Asn Thr SerGln Lys Cys Asp Trp Lys Val Asp Cys Arg Asp Ser Ser 160 165 170 GAT GAAATC AAC TGC ACT GAG ATA TGC TTG CAC AAT GAG TTT TCA TGT 637 Asp Glu IleAsn Cys Thr Glu Ile Cys Leu His Asn Glu Phe Ser Cys 175 180 185 190 GGCAAT GGA GAG TGT ATC CCT CGT GCT TAT GTC TGT GAC CAT GAC AAT 685 Gly AsnGly Glu Cys Ile Pro Arg Ala Tyr Val Cys Asp His Asp Asn 195 200 205 GATTGC CAA GAC GGC AGT GAY GAA CAT GCT TGC AAC TAT CCG ACC TGC 733 Asp CysGln Asp Gly Ser Asp Glu His Ala Cys Asn Tyr Pro Thr Cys 210 215 220 GGTGGT TAC CAG TTC ACT TGC CCC AGT GGC CGA TGC ATT TAT CAA AAC 781 Gly GlyTyr Gln Phe Thr Cys Pro Ser Gly Arg Cys Ile Tyr Gln Asn 225 230 235 TGGGTT TGT GAT GGA GAA GAT GAC TGT AAA GAT AAT GGA GAT GAA GAT 829 Trp ValCys Asp Gly Glu Asp Asp Cys Lys Asp Asn Gly Asp Glu Asp 240 245 250 GGATGT GAA AGC GGT CCT CAT GAT GTT CAT AAA TGT TCC CCA AGA GAA 877 Gly CysGlu Ser Gly Pro His Asp Val His Lys Cys Ser Pro Arg Glu 255 260 265 270TGG TCT TGC CCA GAG TCG GGA CGA TGC ATC TCC ATT TAT AAA GTT TGT 925 TrpSer Cys Pro Glu Ser Gly Arg Cys Ile Ser Ile Tyr Lys Val Cys 275 280 285GAT GGG ATT TTA GAT TGC CCA GGA AGA GAA GAT GAA AAC AAC ACT AGT 973 AspGly Ile Leu Asp Cys Pro Gly Arg Glu Asp Glu Asn Asn Thr Ser 290 295 300ACC GGA AAA TAC TGT AGT ATG ACT CTG TGC TCT GCC TTG AAC TGC CAG 1021 ThrGly Lys Tyr Cys Ser Met Thr Leu Cys Ser Ala Leu Asn Cys Gln 305 310 315TAC CAG TGC CAT GAG ACG CCG TAT GGA GGA GCG TGT TTT TGT CCC CCA 1069 TyrGln Cys His Glu Thr Pro Tyr Gly Gly Ala Cys Phe Cys Pro Pro 320 325 330GGT TAT ATC ATC AAC CAC AAT GAC AGC CGT ACC TGT GTT GAG TTT GAT 1117 GlyTyr Ile Ile Asn His Asn Asp Ser Arg Thr Cys Val Glu Phe Asp 335 340 345350 GAT TGC CAG ATA TGG GGA ATT TGT GAC CAG AAG TGT GAA AGC CGA CCT 1165Asp Cys Gln Ile Trp Gly Ile Cys Asp Gln Lys Cys Glu Ser Arg Pro 355 360365 GGC CGT CAC CTG TGC CAC TGT GAA GAA GGG TAT ATC TTG GAG CGT GGA 1213Gly Arg His Leu Cys His Cys Glu Glu Gly Tyr Ile Leu Glu Arg Gly 370 375380 CAG TAT TGC AAA GCT AAT GAT TCC TTT GGC GAG GCC TCC ATT ATC TTC 1261Gln Tyr Cys Lys Ala Asn Asp Ser Phe Gly Glu Ala Ser Ile Ile Phe 385 390395 TCC AAT GGT CGG GAT TTG TTA ATT GGT GAT ATT CAT GGA AGG AGC TTC 1309Ser Asn Gly Arg Asp Leu Leu Ile Gly Asp Ile His Gly Arg Ser Phe 400 405410 CGG ATC CTA GTG GAG TCT CAG AAT CGT GGA GTG GCC GTG GGT GTG GCT 1357Arg Ile Leu Val Glu Ser Gln Asn Arg Gly Val Ala Val Gly Val Ala 415 420425 430 TTC CAC TAT CAC CTG CAA AGA GTT TTT TGG ACA GAC ACC GTG CAA AAT1405 Phe His Tyr His Leu Gln Arg Val Phe Trp Thr Asp Thr Val Gln Asn 435440 445 AAG GTT TTT TCA GTT GAC ATT AAT GGT TTA AAT ATC CAA GAG GTT CTC1453 Lys Val Phe Ser Val Asp Ile Asn Gly Leu Asn Ile Gln Glu Val Leu 450455 460 AAT GTT TCT GTT GAA ACC CCA GAG AAC CTG GCT GTG GAC TGG GTT AAT1501 Asn Val Ser Val Glu Thr Pro Glu Asn Leu Ala Val Asp Trp Val Asn 465470 475 AAT AAA ATC TAT CTA GTG GAA ACC AAG GTC AAC CGC ATA GAT ATG GTA1549 Asn Lys Ile Tyr Leu Val Glu Thr Lys Val Asn Arg Ile Asp Met Val 480485 490 AAT TTG GAT GGA AGC TAT CGG GTT ACC CTT ATA ACT GAA AAC TTG GGG1597 Asn Leu Asp Gly Ser Tyr Arg Val Thr Leu Ile Thr Glu Asn Leu Gly 495500 505 510 CAT CCT AGA GGA ATT GCC GTG GAC CCA ACT GTT GGT TAT TTA TTTTTC 1645 His Pro Arg Gly Ile Ala Val Asp Pro Thr Val Gly Tyr Leu Phe Phe515 520 525 TCA GAT TGG GAG AGC CTT TCT GGG GAA CCT AAG CTG GAA AGG GCATTC 1693 Ser Asp Trp Glu Ser Leu Ser Gly Glu Pro Lys Leu Glu Arg Ala Phe530 535 540 ATG GAT GGC AGC AAC CGT AAA GAC TTG GTG AAA ACA AAG CTG GGATGG 1741 Met Asp Gly Ser Asn Arg Lys Asp Leu Val Lys Thr Lys Leu Gly Trp545 550 555 CCT GCT GGG GTA ACT CTG GAT ATG ATA TCG AAG CGT GTT TAC TGGGTT 1789 Pro Ala Gly Val Thr Leu Asp Met Ile Ser Lys Arg Val Tyr Trp Val560 565 570 GAC TCT CGG TTT GAT TAC ATT GAA ACT GTA ACT TAT GAT GGA ATTCAA 1837 Asp Ser Arg Phe Asp Tyr Ile Glu Thr Val Thr Tyr Asp Gly Ile Gln575 580 585 590 AGG AAG ACT GTA GTT CAT GGA GGC TCC CTC ATT CCT CAT CCCTTT GGA 1885 Arg Lys Thr Val Val His Gly Gly Ser Leu Ile Pro His Pro PheGly 595 600 605 GTA AGC TTA TTT GAA GGT CAG GTG TTC TTT ACA GAT TGG ACAAAG ATG 1933 Val Ser Leu Phe Glu Gly Gln Val Phe Phe Thr Asp Trp Thr LysMet 610 615 620 GCC GTG CTG AAG GCA AAC AAG TTC ACA GAG ACC AAC CCA CAAGTG TAC 1981 Ala Val Leu Lys Ala Asn Lys Phe Thr Glu Thr Asn Pro Gln ValTyr 625 630 635 TAC CAG GCT TCC CTG AGG CCC TAT GGA GTG ACT GTT TAC CATTCC CTC 2029 Tyr Gln Ala Ser Leu Arg Pro Tyr Gly Val Thr Val Tyr His SerLeu 640 645 650 AGA CAG CCC TAT GCT ACC AAT CCG TGT AAA GAT AAC AAT GGGGGC TGT 2077 Arg Gln Pro Tyr Ala Thr Asn Pro Cys Lys Asp Asn Asn Gly GlyCys 655 660 665 670 GAG CAG GTC TGT GTY CTC AGC CAC AGA ACA GAT AAT GATGGT TTG GGT 2125 Glu Gln Val Cys Val Leu Ser His Arg Thr Asp Asn Asp GlyLeu Gly 675 680 685 TTC CGT TGC AAG TGC ACA TTC GGC TTC CAA CTG GAT ACAGAT GAG CGC 2173 Phe Arg Cys Lys Cys Thr Phe Gly Phe Gln Leu Asp Thr AspGlu Arg 690 695 700 CAC TGC ATT GCT GTT CAG AAT TTC CTC ATT TTT TCA TCCCAA GTT GCT 2221 His Cys Ile Ala Val Gln Asn Phe Leu Ile Phe Ser Ser GlnVal Ala 705 710 715 ATT CGT GGG ATC CCG TTC ACC TTG TCT ACC CAG GAA GATGTC ATG GTT 2269 Ile Arg Gly Ile Pro Phe Thr Leu Ser Thr Gln Glu Asp ValMet Val 720 725 730 CCA GTT TCG GGG AAT CCT TCT TTC TTT GTC GGG ATT GATTTT GAC GCC 2317 Pro Val Ser Gly Asn Pro Ser Phe Phe Val Gly Ile Asp PheAsp Ala 735 740 745 750 CAG GAC AGC ACT ATC TTT TTT TCA GAT ATG TCA AAACAC ATG ATT TTT 2365 Gln Asp Ser Thr Ile Phe Phe Ser Asp Met Ser Lys HisMet Ile Phe 755 760 765 AAG CAA AAG ATT GAT GGC ACA GGA AGA GAA ATT CTCGCA GCT AAC AGG 2413 Lys Gln Lys Ile Asp Gly Thr Gly Arg Glu Ile Leu AlaAla Asn Arg 770 775 780 GTG GAA AAT GTT GAA AGT TTG GCT TTT GAC TGG ATTTCA AAG AAT CTC 2461 Val Glu Asn Val Glu Ser Leu Ala Phe Asp Trp Ile SerLys Asn Leu 785 790 795 TAT TGG ACA GAC TCT CAT TAC AAG AGT ATC AGT GTCATG AGG CTA GCT 2509 Tyr Trp Thr Asp Ser His Tyr Lys Ser Ile Ser Val MetArg Leu Ala 800 805 810 GAT AAA ACG AGA CGC ACG GTA GTT CAG TAT TTA AATAAC CCA CGG TCG 2557 Asp Lys Thr Arg Arg Thr Val Val Gln Tyr Leu Asn AsnPro Arg Ser 815 820 825 830 GTG GTA GTT CAT CCT TTT GCC GGG TAT CTA TTCTTC ACT GAT TGG TTC 2605 Val Val Val His Pro Phe Ala Gly Tyr Leu Phe PheThr Asp Trp Phe 835 840 845 CGT CCT GCT AAA ATT ATG AGA GCA TGG AGT GACGGA TCT CAC CTC TTG 2653 Arg Pro Ala Lys Ile Met Arg Ala Trp Ser Asp GlySer His Leu Leu 850 855 860 CCT GTA ATA AAC ACT ACT CTT GGA TGG CCC AATGGC TTG GCC ATC GAT 2701 Pro Val Ile Asn Thr Thr Leu Gly Trp Pro Asn GlyLeu Ala Ile Asp 865 870 875 TGG GCT GCT TCA CGA TTG TAC TGG GTA GAT GCCTAT TTT GAT AAA ATT 2749 Trp Ala Ala Ser Arg Leu Tyr Trp Val Asp Ala TyrPhe Asp Lys Ile 880 885 890 GAG CAC AGC ACC TTT GAT GGT TTA GAC AGA AGAAGA CTG GGC CAT ATA 2797 Glu His Ser Thr Phe Asp Gly Leu Asp Arg Arg ArgLeu Gly His Ile 895 900 905 910 GAG CAG ATG ACA CAT CCG TTT GGA CTT GCCATC TTT GGA GAG CAT TTA 2845 Glu Gln Met Thr His Pro Phe Gly Leu Ala IlePhe Gly Glu His Leu 915 920 925 TTT TTT ACT GAC TGG AGA CTG GGT GCC ATTATT CGA GTC AGG AAA GCA 2893 Phe Phe Thr Asp Trp Arg Leu Gly Ala Ile IleArg Val Arg Lys Ala 930 935 940 GAT GGT GGA GAA ATG ACA GTT ATC CGA AGTGGC ATT GCT TAC ATA CTG 2941 Asp Gly Gly Glu Met Thr Val Ile Arg Ser GlyIle Ala Tyr Ile Leu 945 950 955 CAT TTG AAA TCG TAT GAT GTC AAC ATC CAGACT GGT TCT AAC GCC TGT 2989 His Leu Lys Ser Tyr Asp Val Asn Ile Gln ThrGly Ser Asn Ala Cys 960 965 970 AAT CAA CCC ACG CAT CCT AAC GGT GAC TGCAGC CAC TTC TGC TTC CCG 3037 Asn Gln Pro Thr His Pro Asn Gly Asp Cys SerHis Phe Cys Phe Pro 975 980 985 990 GTG CCA AAT TTC CAG CGA GTG TGT GGGTGC CCT TAT GGA ATG AGG CTG 3085 Val Pro Asn Phe Gln Arg Val Cys Gly CysPro Tyr Gly Met Arg Leu 995 1000 1005 GCT TCC AAT CAC TTG ACA TGC GAGGGG GAC CCA ACA AAT GAA CCA CCC 3133 Ala Ser Asn His Leu Thr Cys Glu GlyAsp Pro Thr Asn Glu Pro Pro 1010 1015 1020 ACG GAG CAG TGT GGC TTA TTTTCC TTC CCC TGT AAA AAT GGC AGA TGT 3181 Thr Glu Gln Cys Gly Leu Phe SerPhe Pro Cys Lys Asn Gly Arg Cys 1025 1030 1035 GTG CCC AAT TAC TAT CTCTGT GAT GGA GTC GAT GAT TGT CAT GAT AAC 3229 Val Pro Asn Tyr Tyr Leu CysAsp Gly Val Asp Asp Cys His Asp Asn 1040 1045 1050 AGT GAT GAG CAA CTATGT GGC ACA CTT AAT AAT ACC TGT TCA TCT TCG 3277 Ser Asp Glu Gln Leu CysGly Thr Leu Asn Asn Thr Cys Ser Ser Ser 1055 1060 1065 1070 GCG TTC ACCTGT GGC CAT GGG GAG TGC ATT CCT GCA CAC TGG CGC TGT 3325 Ala Phe Thr CysGly His Gly Glu Cys Ile Pro Ala His Trp Arg Cys 1075 1080 1085 GAC AAACGC AAC GAC TGT GTG GAT GGC AGT GAT GAG CAC AAC TGC CCC 3373 Asp Lys ArgAsn Asp Cys Val Asp Gly Ser Asp Glu His Asn Cys Pro 1090 1095 1100 ACCCAC GCA CCT GCT TCC TGC CTT GAC ACC CAA TAC ACC TGT GAT AAT 3421 Thr HisAla Pro Ala Ser Cys Leu Asp Thr Gln Tyr Thr Cys Asp Asn 1105 1110 1115CAC CAG TGT ATC TCA AAG AAC TGG GTC TGT GAC ACA GAC AAT GAT TGT 3469 HisGln Cys Ile Ser Lys Asn Trp Val Cys Asp Thr Asp Asn Asp Cys 1120 11251130 GGG GAT GGA TCT GAT GAA AAG AAC TGC AAT TCG ACA GAG ACA TGC CAA3517 Gly Asp Gly Ser Asp Glu Lys Asn Cys Asn Ser Thr Glu Thr Cys Gln1135 1140 1145 1150 CCT AGT CAG TTT AAT TGC CCC AAT CAT CGA TGT ATT GACCTA TCG TTT 3565 Pro Ser Gln Phe Asn Cys Pro Asn His Arg Cys Ile Asp LeuSer Phe 1155 1160 1165 GTC TGT GAT GGT GAC AAG GAT TGT GTT GAT GGA TCTGAT GAG GTT GGT 3613 Val Cys Asp Gly Asp Lys Asp Cys Val Asp Gly Ser AspGlu Val Gly 1170 1175 1180 TGT GTA TTA AAC TGT ACT GCT TCT CAA TTC AAGTGT GCC AGT GGG GAT 3661 Cys Val Leu Asn Cys Thr Ala Ser Gln Phe Lys CysAla Ser Gly Asp 1185 1190 1195 AAA TGT ATT GGC GTC ACA AAT CGT TGT GATGGT GTT TTT GAT TGC AGT 3709 Lys Cys Ile Gly Val Thr Asn Arg Cys Asp GlyVal Phe Asp Cys Ser 1200 1205 1210 GAC AAC TCG GAT GAA GCG GGC TGT CCAACC AGG CCT CCT GGT ATG TGC 3757 Asp Asn Ser Asp Glu Ala Gly Cys Pro ThrArg Pro Pro Gly Met Cys 1215 1220 1225 1230 CAC TCA GAT GAA TTT CAG TGCCAA GAA GAT GGT ATC TGC ATC CCG AAC 3805 His Ser Asp Glu Phe Gln Cys GlnGlu Asp Gly Ile Cys Ile Pro Asn 1235 1240 1245 TTC TGG GAA TGT GAT GGGCAT CCA GAC TGC CTC TAT GGA TCT GAT GAG 3853 Phe Trp Glu Cys Asp Gly HisPro Asp Cys Leu Tyr Gly Ser Asp Glu 1250 1255 1260 CAC AAT GCC TGT GTCCCC AAG ACT TGC CCH TCA TCA TAT TTC CAC TGT 3901 His Asn Ala Cys Val ProLys Thr Cys Pro Ser Ser Tyr Phe His Cys 1265 1270 1275 GAC AAC GGA AACTGC ATC CAC AGG SCA TGG CTC TGT GAT CGG GAC AAT 3949 Asp Asn Gly Asn CysIle His Arg Xaa Trp Leu Cys Asp Arg Asp Asn 1280 1285 1290 GAC TGC GGGGAT ATG AGT GAT GAG AAG GAC TGC CCT ACT CAG CCC TTT 3997 Asp Cys Gly AspMet Ser Asp Glu Lys Asp Cys Pro Thr Gln Pro Phe 1295 1300 1305 1310 CGCTGT CCT AGT TGG CAA TGG CAG TGT CTT GGC CAT AAC ATC TGT GTG 4045 Arg CysPro Ser Trp Gln Trp Gln Cys Leu Gly His Asn Ile Cys Val 1315 1320 1325AAT CTG AGT GTA GTG TGT GAT GGC ATC TTT GAC TGC CCC AAT GGG ACA 4093 AsnLeu Ser Val Val Cys Asp Gly Ile Phe Asp Cys Pro Asn Gly Thr 1330 13351340 GAT GAG TCC CCA CTT TGC AAT GGG AAC AGC TGC TCA GAT TTC AAT GGT4141 Asp Glu Ser Pro Leu Cys Asn Gly Asn Ser Cys Ser Asp Phe Asn Gly1345 1350 1355 GGT TGT ACT CAC GAG TGT GTT CAA GAG CCC TTT GGG GCT AAATGC CTA 4189 Gly Cys Thr His Glu Cys Val Gln Glu Pro Phe Gly Ala Lys CysLeu 1360 1365 1370 TGT CCA TTG GGA TTC TTA CTT GCC AAT GAT TCT AAG ACCTGT GAA GAC 4237 Cys Pro Leu Gly Phe Leu Leu Ala Asn Asp Ser Lys Thr CysGlu Asp 1375 1380 1385 1390 ATA GAT GAA TGT GAT ATT CTA GGC TCT TGT AGCCAG CAC TGT TAC AAT 4285 Ile Asp Glu Cys Asp Ile Leu Gly Ser Cys Ser GlnHis Cys Tyr Asn 1395 1400 1405 ATG AGA GGT TCT TTC CGG TGC TCG TGT GATACA GGC TAC ATG TTA GAA 4333 Met Arg Gly Ser Phe Arg Cys Ser Cys Asp ThrGly Tyr Met Leu Glu 1410 1415 1420 AGT GAT GGG AGG ACT TGC AAA GTT ACAGCA TCT GAG AGT CTG CTG TTA 4381 Ser Asp Gly Arg Thr Cys Lys Val Thr AlaSer Glu Ser Leu Leu Leu 1425 1430 1435 CTT GTG GCA AGT CAG AAC AAA ATTATT GCC GAC AGT GTC ACC TCC CAG 4429 Leu Val Ala Ser Gln Asn Lys Ile IleAla Asp Ser Val Thr Ser Gln 1440 1445 1450 GTC CAC AAT ATC TAT TCA TTGGTC GAG AAT GGT TCT TAC ATT GTA GCT 4477 Val His Asn Ile Tyr Ser Leu ValGlu Asn Gly Ser Tyr Ile Val Ala 1455 1460 1465 1470 GTT GAT TTT GAT TCAATT AGT GGT CGT ATC TTT TGG TCT GAT GCA ACT 4525 Val Asp Phe Asp Ser IleSer Gly Arg Ile Phe Trp Ser Asp Ala Thr 1475 1480 1485 CAG GGT AAA ACCTGG AGT GCG TTT CAA AAT GGA ACG GAC AGA AGA GTG 4573 Gln Gly Lys Thr TrpSer Ala Phe Gln Asn Gly Thr Asp Arg Arg Val 1490 1495 1500 GTA TTT GACAGT AGC ATC ATC TTG ACT GAA ACT ATT GCA ATA GAT TGG 4621 Val Phe Asp SerSer Ile Ile Leu Thr Glu Thr Ile Ala Ile Asp Trp 1505 1510 1515 GTA GGTCGT AAT CTT TAC TGG ACA GAC TAT GCT CTG GAA ACA ATT GAA 4669 Val Gly ArgAsn Leu Tyr Trp Thr Asp Tyr Ala Leu Glu Thr Ile Glu 1520 1525 1530 GTCTCC AAA ATT GAT GGG AGC CAC AGG ACT GTG CTG ATT AGT AAA AAC 4717 Val SerLys Ile Asp Gly Ser His Arg Thr Val Leu Ile Ser Lys Asn 1535 1540 15451550 CTA ACA AAT CCA AGA GGA CTA GCA TTA GAT CCC AGA ATG AAT GAG CAT4765 Leu Thr Asn Pro Arg Gly Leu Ala Leu Asp Pro Arg Met Asn Glu His1555 1560 1565 CTA CTG TTC TGG TCT GAC TGG GGC CAC CAC CCT CGC ATC GAGCGA GCC 4813 Leu Leu Phe Trp Ser Asp Trp Gly His His Pro Arg Ile Glu ArgAla 1570 1575 1580 AGC ATG GAC GGC AGC ATG CGC ACT GTC ATT GTC CAG GACAAG ATC TTC 4861 Ser Met Asp Gly Ser Met Arg Thr Val Ile Val Gln Asp LysIle Phe 1585 1590 1595 TGG CCC TGC GGC TTA ACT ATT GAC TAC CCC AAC AGACTG CTC TAC TTC 4909 Trp Pro Cys Gly Leu Thr Ile Asp Tyr Pro Asn Arg LeuLeu Tyr Phe 1600 1605 1610 ATG GAC TCC TAT CTT GAT TAC ATG GAC TTT TGCGAT TAT AAT GGA CAC 4957 Met Asp Ser Tyr Leu Asp Tyr Met Asp Phe Cys AspTyr Asn Gly His 1615 1620 1625 1630 CAT CGG AGA CAG GTG ATA GCC AGT GATTTG ATT ATA CGG CAC CCC TAT 5005 His Arg Arg Gln Val Ile Ala Ser Asp LeuIle Ile Arg His Pro Tyr 1635 1640 1645 GCC CTA ACT CTC TTT GAA GAC TCTGTG TAC TGG ACT GAC CGT GCT ACT 5053 Ala Leu Thr Leu Phe Glu Asp Ser ValTyr Trp Thr Asp Arg Ala Thr 1650 1655 1660 CGT CGG GTT ATG CGA GCC AACAAG TGG CAT GGA GGG AAC CAG TCA GTT 5101 Arg Arg Val Met Arg Ala Asn LysTrp His Gly Gly Asn Gln Ser Val 1665 1670 1675 GTA ATG TAT AAT ATT CAATGG CCC CTT GGG ATT GTT GCG GTT CAT CCT 5149 Val Met Tyr Asn Ile Gln TrpPro Leu Gly Ile Val Ala Val His Pro 1680 1685 1690 TCG AAA CAA CCA AATTCT GTG AAT CCA TGT GCC TTT TCC CGC TGC AGC 5197 Ser Lys Gln Pro Asn SerVal Asn Pro Cys Ala Phe Ser Arg Cys Ser 1695 1700 1705 1710 CAT CTC TGCCTG CTT TCC TCA CAG GGG CCT CAT TTT TAC TCC TGT GTT 5245 His Leu Cys LeuLeu Ser Ser Gln Gly Pro His Phe Tyr Ser Cys Val 1715 1720 1725 TGT CCTTCA GGA TGG AGT CTG TCT CCT GAT CTC CTG AAT TGC TTG AGA 5293 Cys Pro SerGly Trp Ser Leu Ser Pro Asp Leu Leu Asn Cys Leu Arg 1730 1735 1740 GATGAT CAA CCT TTC TTA ATA ACT GTA AGG CAA CAT ATA ATT TTT GGA 5341 Asp AspGln Pro Phe Leu Ile Thr Val Arg Gln His Ile Ile Phe Gly 1745 1750 1755ATC TCC CTT AAT CCT GAG GTG AAG AGC AAT GAT GCT ATG GTC CCC ATA 5389 IleSer Leu Asn Pro Glu Val Lys Ser Asn Asp Ala Met Val Pro Ile 1760 17651770 GCA GGG ATA CAG AAT GGT TTA GAT GTT GAA TTT GAT GAT GCT GAG CAA5437 Ala Gly Ile Gln Asn Gly Leu Asp Val Glu Phe Asp Asp Ala Glu Gln1775 1780 1785 1790 TAC ATC TAT TGG GTT GAA AAT CCA GGT GAA ATT CAC AGAGTG AAG ACA 5485 Tyr Ile Tyr Trp Val Glu Asn Pro Gly Glu Ile His Arg ValLys Thr 1795 1800 1805 GAT GGC ACC AAC AGG ACA GTA TTT GCT TCT ATA TCTATG GTG GGG CCT 5533 Asp Gly Thr Asn Arg Thr Val Phe Ala Ser Ile Ser MetVal Gly Pro 1810 1815 1820 TCT ATG AAC CTG GCC TTA GAT TGG ATT TCA AGAAAC CTT TAT TCT ACC 5581 Ser Met Asn Leu Ala Leu Asp Trp Ile Ser Arg AsnLeu Tyr Ser Thr 1825 1830 1835 AAT CCT AGA ACT CAG TCA ATC GAG GTT TTGACA CTC CAC GGA GAT ATC 5629 Asn Pro Arg Thr Gln Ser Ile Glu Val Leu ThrLeu His Gly Asp Ile 1840 1845 1850 AGA TAC AGA AAA ACA TTG ATT GCC AATGAT GGG ACA GCT CTT GGA GTT 5677 Arg Tyr Arg Lys Thr Leu Ile Ala Asn AspGly Thr Ala Leu Gly Val 1855 1860 1865 1870 GGC TTT CCA ATT GGC ATA ACTGTT GAT CCT GCT CGT GGG AAG CTG TAC 5725 Gly Phe Pro Ile Gly Ile Thr ValAsp Pro Ala Arg Gly Lys Leu Tyr 1875 1880 1885 TGG TCA GAC CAA GGA ACTGAC AGT GGG GTT CCT GCC AAG ATC GCC AGT 5773 Trp Ser Asp Gln Gly Thr AspSer Gly Val Pro Ala Lys Ile Ala Ser 1890 1895 1900 GCT AAC ATG GAT GGCACA TCT GTG AAA ACT CTC TTT ACT GGG AAC CTC 5821 Ala Asn Met Asp Gly ThrSer Val Lys Thr Leu Phe Thr Gly Asn Leu 1905 1910 1915 GAA CAC CTG GAGTGT GTC ACT CTT GAC ATC GAA GAG CAG AAA CTC TAC 5869 Glu His Leu Glu CysVal Thr Leu Asp Ile Glu Glu Gln Lys Leu Tyr 1920 1925 1930 TGG GCA GTCACT GGA AGA GGA GTG ATT GAA AGA GGA AAC GTG GAT GGA 5917 Trp Ala Val ThrGly Arg Gly Val Ile Glu Arg Gly Asn Val Asp Gly 1935 1940 1945 1950 ACAGAT CGG ATG ATC CTG GTA CAC CAG CTT TCC CAC CCC TGG GGA ATT 5965 Thr AspArg Met Ile Leu Val His Gln Leu Ser His Pro Trp Gly Ile 1955 1960 1965GCA GTC CAT GAT TCT TTC CTT TAT TAT ACT GAT GAA CAG TAT GAG GTC 6013 AlaVal His Asp Ser Phe Leu Tyr Tyr Thr Asp Glu Gln Tyr Glu Val 1970 19751980 ATT GAA AGA GTT GAT AAG GCC ACT GGG GCC AAC AAA ATA GTC TTG AGA6061 Ile Glu Arg Val Asp Lys Ala Thr Gly Ala Asn Lys Ile Val Leu Arg1985 1990 1995 GAT AAT GTT CCA AAT CTG AGG GGT CTT CAA GTT TAT CAC AGACGC AAT 6109 Asp Asn Val Pro Asn Leu Arg Gly Leu Gln Val Tyr His Arg ArgAsn 2000 2005 2010 GCC GCC GAA TCC TCA AAT GGC TGT AGC AAC AAC ATG AATGCC TGT CAG 6157 Ala Ala Glu Ser Ser Asn Gly Cys Ser Asn Asn Met Asn AlaCys Gln 2015 2020 2025 2030 CAG ATT TGC CTG CCT GTA CCA GGA GGA TTG TTTTCC TGC GCC TGT GCC 6205 Gln Ile Cys Leu Pro Val Pro Gly Gly Leu Phe SerCys Ala Cys Ala 2035 2040 2045 ACT GGA TTT AAA CTC AAT CCT GAT AAT CGGTCC TGC TCT CCA TAT AAC 6253 Thr Gly Phe Lys Leu Asn Pro Asp Asn Arg SerCys Ser Pro Tyr Asn 2050 2055 2060 TCT TTC ATT GTT GTT TCA ATG CTG TCTGCA ATC AGA GGC TTT AGC TTG 6301 Ser Phe Ile Val Val Ser Met Leu Ser AlaIle Arg Gly Phe Ser Leu 2065 2070 2075 GAA TTG TCA GAT CAT TCA GAA ACCATG GTG CCG GTG GCA GGC CAA GGA 6349 Glu Leu Ser Asp His Ser Glu Thr MetVal Pro Val Ala Gly Gln Gly 2080 2085 2090 CGA AAC GCA CTG CAT GTG GATGTG GAT GTG TCC TCT GGC TTT ATT TAT 6397 Arg Asn Ala Leu His Val Asp ValAsp Val Ser Ser Gly Phe Ile Tyr 2095 2100 2105 2110 TGG TGT GAT TTT AGCAGC TCA GTG GCA TCT GAT AAT GCG ATC CGT AGA 6445 Trp Cys Asp Phe Ser SerSer Val Ala Ser Asp Asn Ala Ile Arg Arg 2115 2120 2125 ATT AAA CCA GATGGA TCT TCT CTG ATG AAC ATT GTG ACA CAT GGA ATA 6493 Ile Lys Pro Asp GlySer Ser Leu Met Asn Ile Val Thr His Gly Ile 2130 2135 2140 GGA GAA AATGGA GTC CGG GGT ATT GCA GTG GAT TGG GTA GCA GGA AAT 6541 Gly Glu Asn GlyVal Arg Gly Ile Ala Val Asp Trp Val Ala Gly Asn 2145 2150 2155 CTT TATTTC ACC AAT GCC TTT GTT TCT GAA ACA CTG ATA GAA GTT CTG 6589 Leu Tyr PheThr Asn Ala Phe Val Ser Glu Thr Leu Ile Glu Val Leu 2160 2165 2170 CGGATC AAT ACT ACT TAC CGC CGT GTT CTT CTT AAA GTC ACA GTG GAC 6637 Arg IleAsn Thr Thr Tyr Arg Arg Val Leu Leu Lys Val Thr Val Asp 2175 2180 21852190 ATG CCT AGG CAT ATT GTT GTA GAT CCC AAG AAC AGA TAC CTC TTC TGG6685 Met Pro Arg His Ile Val Val Asp Pro Lys Asn Arg Tyr Leu Phe Trp2195 2200 2205 GCT GAC TAT GGG CAG AGA CCA AAG ATT GAG CGT TCT TTC CTTGAC TGT 6733 Ala Asp Tyr Gly Gln Arg Pro Lys Ile Glu Arg Ser Phe Leu AspCys 2210 2215 2220 ACC AAT CGA ACA GTG CTT GTG TCA GAG GGC ATT GTC ACACCA CGG GGC 6781 Thr Asn Arg Thr Val Leu Val Ser Glu Gly Ile Val Thr ProArg Gly 2225 2230 2235 TTG GCA GTG GAC CGA AGT GAT GGC TAC GTT TAT TGGGTT GAT GAT TCT 6829 Leu Ala Val Asp Arg Ser Asp Gly Tyr Val Tyr Trp ValAsp Asp Ser 2240 2245 2250 TTA GAT ATA ATT GCA AGG ATT CGT ATC AAT GGAGAG AAC TCT GAA GTG 6877 Leu Asp Ile Ile Ala Arg Ile Arg Ile Asn Gly GluAsn Ser Glu Val 2255 2260 2265 2270 ATT CGT TAT GGC AGT CGT TAC CCA ACTCCT TAT GGC ATC ACT GTT TTT 6925 Ile Arg Tyr Gly Ser Arg Tyr Pro Thr ProTyr Gly Ile Thr Val Phe 2275 2280 2285 GAA AAT TCT ATC ATA TGG GTA GATAGG AAT TTG AAA AAG ATC TTC CAA 6973 Glu Asn Ser Ile Ile Trp Val Asp ArgAsn Leu Lys Lys Ile Phe Gln 2290 2295 2300 GCC AGC AAG GAA CCA GAG AACACA GAG CCA CCC ACA GTG ATA AGA GAC 7021 Ala Ser Lys Glu Pro Glu Asn ThrGlu Pro Pro Thr Val Ile Arg Asp 2305 2310 2315 AAT ATC AAC TGG CTA AGAGAT GTG ACC ATC TTT GAC AAG CAA GTC CAG 7069 Asn Ile Asn Trp Leu Arg AspVal Thr Ile Phe Asp Lys Gln Val Gln 2320 2325 2330 CCC CGG TCA CCA GCAGAG GTC AAC AAC AAC CCT TGC TTG GAA AAC AAT 7117 Pro Arg Ser Pro Ala GluVal Asn Asn Asn Pro Cys Leu Glu Asn Asn 2335 2340 2345 2350 GGT GGG TGCTCT CAT CTC TGC TTT GCT CTG CCT GGA TTG CAC ACC CCA 7165 Gly Gly Cys SerHis Leu Cys Phe Ala Leu Pro Gly Leu His Thr Pro 2355 2360 2365 AAA TGTGAC TGT GCC TTT GGG ACC CTG CAA AGT GAT GGC AAG AAT TGT 7213 Lys Cys AspCys Ala Phe Gly Thr Leu Gln Ser Asp Gly Lys Asn Cys 2370 2375 2380 GCCATT TCA ACA GAA AAT TTC CTC ATC TTT GCC TTG TCT AAT TCC TTG 7261 Ala IleSer Thr Glu Asn Phe Leu Ile Phe Ala Leu Ser Asn Ser Leu 2385 2390 2395AGA AGC TTA CAC TTG GAC CCT GAA AAC CAT AGC CCA CCT TTC CAA ACA 7309 ArgSer Leu His Leu Asp Pro Glu Asn His Ser Pro Pro Phe Gln Thr 2400 24052410 ATA AAT GTG GAA AGA ACT GTC ATG TCT CTA GAC TAT GAC AGT GTA AGT7357 Ile Asn Val Glu Arg Thr Val Met Ser Leu Asp Tyr Asp Ser Val Ser2415 2420 2425 2430 GAT AGA ATC TAC TTC ACA CAA AAT TTA GCC TCT GGA GTTGGA CAG ATT 7405 Asp Arg Ile Tyr Phe Thr Gln Asn Leu Ala Ser Gly Val GlyGln Ile 2435 2440 2445 TCC TAT GCC ACC CTG TCT TCA GGG ATC CAT ACT CCAACT GTC ATT GCT 7453 Ser Tyr Ala Thr Leu Ser Ser Gly Ile His Thr Pro ThrVal Ile Ala 2450 2455 2460 TCA GGT ATA GGG ACT GCT GAT GGC ATT GCC TTTGAC TGG ATT ACT AGA 7501 Ser Gly Ile Gly Thr Ala Asp Gly Ile Ala Phe AspTrp Ile Thr Arg 2465 2470 2475 AGA ATT TAT TAC AGT GAC TAC CTC AAC CAGATG ATT AAT TCC ATG GCT 7549 Arg Ile Tyr Tyr Ser Asp Tyr Leu Asn Gln MetIle Asn Ser Met Ala 2480 2485 2490 GAA GAT GGG TCT AAC CGC ACT GTG ATAGCC CGC GTT CCA AAA CCA AGA 7597 Glu Asp Gly Ser Asn Arg Thr Val Ile AlaArg Val Pro Lys Pro Arg 2495 2500 2505 2510 GCA ATT GTG TTA GAT CCC TGCCAA GGG TAC CTG TAC TGG GCT GAC TGG 7645 Ala Ile Val Leu Asp Pro Cys GlnGly Tyr Leu Tyr Trp Ala Asp Trp 2515 2520 2525 GAT ACA CAT GCC AAA ATCGAG AGA GCC ACA TTG GGA GGA AAC TTC CGC 7693 Asp Thr His Ala Lys Ile GluArg Ala Thr Leu Gly Gly Asn Phe Arg 2530 2535 2540 GTA CCC ATT GTG AACAGC AGT CTG GTC ATG CCC AGT GGG CTG ACT CTG 7741 Val Pro Ile Val Asn SerSer Leu Val Met Pro Ser Gly Leu Thr Leu 2545 2550 2555 GAC TAT GAA GAGGAC CTT CTC TAC TGG GTG GAT GCT AGT CTG CAG AGG 7789 Asp Tyr Glu Glu AspLeu Leu Tyr Trp Val Asp Ala Ser Leu Gln Arg 2560 2565 2570 ATT GAA CGCAGC ACT CTG ACG GGC GTG GAT CGT GAA GTC ATT GTC AAT 7837 Ile Glu Arg SerThr Leu Thr Gly Val Asp Arg Glu Val Ile Val Asn 2575 2580 2585 2590 GCAGCC GTT CAT GCT TTT GGC TTG ACT CTC TAT GGC CAG TAT ATT TAC 7885 Ala AlaVal His Ala Phe Gly Leu Thr Leu Tyr Gly Gln Tyr Ile Tyr 2595 2600 2605TGG ACT GAC TTG TAC ACA CAA AGA ATT TAC CGA GCT AAC AAA TAT GAC 7933 TrpThr Asp Leu Tyr Thr Gln Arg Ile Tyr Arg Ala Asn Lys Tyr Asp 2610 26152620 GGG TCA GGT CAG ATT GCA ATG ACC ACA AAT TTG CTC TCC CAG CCC AGG7981 Gly Ser Gly Gln Ile Ala Met Thr Thr Asn Leu Leu Ser Gln Pro Arg2625 2630 2635 GGA ATC AAC ACT GTT GTG AAG AAC CAG AAA CAA CAG TGT AACAAT CCT 8029 Gly Ile Asn Thr Val Val Lys Asn Gln Lys Gln Gln Cys Asn AsnPro 2640 2645 2650 TGT GAA CAG TTT AAT GGG GGC TGC AGC CAT ATC TGT GCACCA GGT CCA 8077 Cys Glu Gln Phe Asn Gly Gly Cys Ser His Ile Cys Ala ProGly Pro 2655 2660 2665 2670 AAT GGT GCC GAG TGC CAG TGT CCA CAT GAG GGCAAC TGG TAT TTG GCC 8125 Asn Gly Ala Glu Cys Gln Cys Pro His Glu Gly AsnTrp Tyr Leu Ala 2675 2680 2685 AAC AAC AGG AAG CAC TGC ATT GTG GAC AATGGT GAA CGA TGT GGT GCA 8173 Asn Asn Arg Lys His Cys Ile Val Asp Asn GlyGlu Arg Cys Gly Ala 2690 2695 2700 TCT TCC TTC ACC TGC TCC AAT GGG CGCTGC ATC TCG GAA GAG TGG AAG 8221 Ser Ser Phe Thr Cys Ser Asn Gly Arg CysIle Ser Glu Glu Trp Lys 2705 2710 2715 TGT GAT AAT GAC AAC GAC TGT GGGGAT GGC AGT GAT GAG ATG GAA AGT 8269 Cys Asp Asn Asp Asn Asp Cys Gly AspGly Ser Asp Glu Met Glu Ser 2720 2725 2730 GTC TGT GCA CTT CAC ACC TGCTCA CCG ACA GCC TTC ACC TGT GCC AAT 8317 Val Cys Ala Leu His Thr Cys SerPro Thr Ala Phe Thr Cys Ala Asn 2735 2740 2745 2750 GGG CGA TGT GTC CAATAC TCT TAC CGC TGT GAT TAC TAC AAT GAC TGT 8365 Gly Arg Cys Val Gln TyrSer Tyr Arg Cys Asp Tyr Tyr Asn Asp Cys 2755 2760 2765 GGT GAT GGC AGTGAT GAG GCA GGG TGC CTG TTC AGG GAC TGC AAT GCC 8413 Gly Asp Gly Ser AspGlu Ala Gly Cys Leu Phe Arg Asp Cys Asn Ala 2770 2775 2780 ACC ACG GAGTTT ATG TGC AAT AAC AGA AGG TGC ATA CCT CGT GAG TTT 8461 Thr Thr Glu PheMet Cys Asn Asn Arg Arg Cys Ile Pro Arg Glu Phe 2785 2790 2795 ATC TGCAAT GGT GTA GAC AAC TGC CAT GAT AAT AAC ACT TCA GAT GAG 8509 Ile Cys AsnGly Val Asp Asn Cys His Asp Asn Asn Thr Ser Asp Glu 2800 2805 2810 AAAAAT TGC CCT GAT CGC ACT TGC CAG TCT GGA TAC ACA AAA TGT CAT 8557 Lys AsnCys Pro Asp Arg Thr Cys Gln Ser Gly Tyr Thr Lys Cys His 2815 2820 28252830 AAT TCA AAT ATT TGT ATT CCT CGC GTT TAT TTG TGT GAC GGA GAC AAT8605 Asn Ser Asn Ile Cys Ile Pro Arg Val Tyr Leu Cys Asp Gly Asp Asn2835 2840 2845 GAC TGT GGA GAT AAC AGT GAT GAA AAC CCT ACT TAT TGC ACCACT CAC 8653 Asp Cys Gly Asp Asn Ser Asp Glu Asn Pro Thr Tyr Cys Thr ThrHis 2850 2855 2860 ACG TGC AGC AGC AGT GAG TTC CAA TGC ACA TCT GGG CGCTGT ATT CCT 8701 Thr Cys Ser Ser Ser Glu Phe Gln Cys Thr Ser Gly Arg CysIle Pro 2865 2870 2875 CAA CAT TGG TAT TGT GAT CAA GAA ACA GAT TGT TTTGAT GCC TCT GAT 8749 Gln His Trp Tyr Cys Asp Gln Glu Thr Asp Cys Phe AspAla Ser Asp 2880 2885 2890 GAA CCT GCC TCT TGT GGT CAC TCT GAG CGA ACATGC CTA GCT GAT GAG 8797 Glu Pro Ala Ser Cys Gly His Ser Glu Arg Thr CysLeu Ala Asp Glu 2895 2900 2905 2910 TTC AAG TGT GAT GGT GGG AGG TGC ATCCCA AGC GAA TGG ATC TGT GAC 8845 Phe Lys Cys Asp Gly Gly Arg Cys Ile ProSer Glu Trp Ile Cys Asp 2915 2920 2925 GGT GAT AAT GAC TGT GGG GAT ATGAGT GAC GAG GAT AAA AGG CAC CAG 8893 Gly Asp Asn Asp Cys Gly Asp Met SerAsp Glu Asp Lys Arg His Gln 2930 2935 2940 TGT CAG AAT CAA AAC TGC TCGGAT TCC GAG TTT CTC TGT GTA AAT GAC 8941 Cys Gln Asn Gln Asn Cys Ser AspSer Glu Phe Leu Cys Val Asn Asp 2945 2950 2955 AGA CCT CCG GAC AGG AGGTGC ATT CCC CAG TCT TGG GTC TGT GAT GGC 8989 Arg Pro Pro Asp Arg Arg CysIle Pro Gln Ser Trp Val Cys Asp Gly 2960 2965 2970 GAT GTG GAT TGT ACTGAC GGC TAC GAT GAG AAT CAG AAT TGC ACC AGG 9037 Asp Val Asp Cys Thr AspGly Tyr Asp Glu Asn Gln Asn Cys Thr Arg 2975 2980 2985 2990 AGA ACT TGCTCT GAA AAT GAA TTC ACC TGT GGT TAC GGA CTG TGT ATC 9085 Arg Thr Cys SerGlu Asn Glu Phe Thr Cys Gly Tyr Gly Leu Cys Ile 2995 3000 3005 CCA AAGATA TTC AGG TGT GAC CGG CAC AAT GAC TGT GGT GAC TAT AGC 9133 Pro Lys IlePhe Arg Cys Asp Arg His Asn Asp Cys Gly Asp Tyr Ser 3010 3015 3020 GACGAG AGG GGC TGC TTA TAC CAG ACT TGC CAA CAG AAT CAG TTT ACC 9181 Asp GluArg Gly Cys Leu Tyr Gln Thr Cys Gln Gln Asn Gln Phe Thr 3025 3030 3035TGT CAG AAC GGG CGC TGC ATT AGT AAA ACC TTC GTC TGT GAT GAG GAT 9229 CysGln Asn Gly Arg Cys Ile Ser Lys Thr Phe Val Cys Asp Glu Asp 3040 30453050 AAT GAC TGT GGA GAC GGA TCT GAT GAG CTG ATG CAC CTG TGC CAC ACC9277 Asn Asp Cys Gly Asp Gly Ser Asp Glu Leu Met His Leu Cys His Thr3055 3060 3065 3070 CCA GAA CCC ACG TGT CCA CCT CAC GAG TTC AAG TGT GACAAT GGG CGC 9325 Pro Glu Pro Thr Cys Pro Pro His Glu Phe Lys Cys Asp AsnGly Arg 3075 3080 3085 TGC ATC GAG ATG ATG AAA CTC TGC AAC CAC CTA GATGAC TGT TTG GAC 9373 Cys Ile Glu Met Met Lys Leu Cys Asn His Leu Asp AspCys Leu Asp 3090 3095 3100 AAC AGC GAT GAG AAA GGC TGT GGC ATT AAT GAATGC CAT GAC CCT TCA 9421 Asn Ser Asp Glu Lys Gly Cys Gly Ile Asn Glu CysHis Asp Pro Ser 3105 3110 3115 ATC AGT GGC TGC GAT CAC AAC TGC ACA GACACC TTA ACC AGT TTC TAT 9469 Ile Ser Gly Cys Asp His Asn Cys Thr Asp ThrLeu Thr Ser Phe Tyr 3120 3125 3130 TGT TCC TGT CGT CCT GGT TAC AAG CTCATG TCT GAC AAG CGG ACT TGT 9517 Cys Ser Cys Arg Pro Gly Tyr Lys Leu MetSer Asp Lys Arg Thr Cys 3135 3140 3145 3150 GTT GAT ATT GAT GAA TGC ACAGAG ATG CCT TTT GTC TGT AGC CAG AAG 9565 Val Asp Ile Asp Glu Cys Thr GluMet Pro Phe Val Cys Ser Gln Lys 3155 3160 3165 TGT GAG AAT GTA ATA GGCTCC TAC ATC TGT AAG TGT GCC CCA GGC TAC 9613 Cys Glu Asn Val Ile Gly SerTyr Ile Cys Lys Cys Ala Pro Gly Tyr 3170 3175 3180 CTC CGA GAA CCA GATGGA AAG ACC TGC CGG CAA AAC AGT AAC ATC GAA 9661 Leu Arg Glu Pro Asp GlyLys Thr Cys Arg Gln Asn Ser Asn Ile Glu 3185 3190 3195 CCC TAT CTC ATTTTT AGC AAC CGT TAC TAT TTG AGA AAT TTA ACT ATA 9709 Pro Tyr Leu Ile PheSer Asn Arg Tyr Tyr Leu Arg Asn Leu Thr Ile 3200 3205 3210 GAT GGC TATTTT TAC TCC CTC ATC TTG GAA GGA CTG GAC AAT GTT GTG 9757 Asp Gly Tyr PheTyr Ser Leu Ile Leu Glu Gly Leu Asp Asn Val Val 3215 3220 3225 3230 GCATTA GAT TTT GAC CGA GTA GAG AAG AGA TTG TAT TGG ATT GAT ACA 9805 Ala LeuAsp Phe Asp Arg Val Glu Lys Arg Leu Tyr Trp Ile Asp Thr 3235 3240 3245CAG AGG CAA GTC ATT GAG AGA ATG TTT CTG AAT AAG ACA AAC AAG GAG 9853 GlnArg Gln Val Ile Glu Arg Met Phe Leu Asn Lys Thr Asn Lys Glu 3250 32553260 ACA ATC ATA AAC CAC AGA CTA CCA GCT GCA GAA AGT CTG GCT GTA GAC9901 Thr Ile Ile Asn His Arg Leu Pro Ala Ala Glu Ser Leu Ala Val Asp3265 3270 3275 TGG GTT TCC AGA AAG CTC TAC TGG TTG GAT GCC CGC CTG GATGGC CTC 9949 Trp Val Ser Arg Lys Leu Tyr Trp Leu Asp Ala Arg Leu Asp GlyLeu 3280 3285 3290 TTT GTC TCT GAC CTC AAT GGT GGA CAC CGC CGC ATG CTGGCC CAG CAC 9997 Phe Val Ser Asp Leu Asn Gly Gly His Arg Arg Met Leu AlaGln His 3295 3300 3305 3310 TGT GTG GAT GCC AAC AAC ACC TTC TGC TTT GATAAT CCC AGA GGA CTT 10045 Cys Val Asp Ala Asn Asn Thr Phe Cys Phe AspAsn Pro Arg Gly Leu 3315 3320 3325 GCC CTT CAC CCT CAA TAT GGG TAC CTCTAC TGG GCA GAC TGG GGT CAC 10093 Ala Leu His Pro Gln Tyr Gly Tyr LeuTyr Trp Ala Asp Trp Gly His 3330 3335 3340 CGC GCA TAC ATT GGG AGA GTAGGC ATG GAT GGA ACC AAC AAG TCT GTG 10141 Arg Ala Tyr Ile Gly Arg ValGly Met Asp Gly Thr Asn Lys Ser Val 3345 3350 3355 ATA ATC TCC ACC AAGTTA GAG TGG CCT AAT GGC ATC ACC ATT GAT TAC 10189 Ile Ile Ser Thr LysLeu Glu Trp Pro Asn Gly Ile Thr Ile Asp Tyr 3360 3365 3370 ACC AAT GATCTA CTC TAC TGG GCA GAT GCC CAC CTG GGT TAC ATA GAG 10237 Thr Asn AspLeu Leu Tyr Trp Ala Asp Ala His Leu Gly Tyr Ile Glu 3375 3380 3385 3390TAC TCT GAT TTG GAG GGC CAC CAT CGA CAC ACG GTG TAT GAT GGG GCA 10285Tyr Ser Asp Leu Glu Gly His His Arg His Thr Val Tyr Asp Gly Ala 33953400 3405 CTG CCT CAC CCT TTC GCT ATT ACC ATT TTT GAA GAC ACT ATT TATTGG 10333 Leu Pro His Pro Phe Ala Ile Thr Ile Phe Glu Asp Thr Ile TyrTrp 3410 3415 3420 ACA GAT TGG AAT ACA AGG ACA GTG GAA AAG GGA AAC AAATAT GAT GGA 10381 Thr Asp Trp Asn Thr Arg Thr Val Glu Lys Gly Asn LysTyr Asp Gly 3425 3430 3435 TCA AAT AGA CAG ACA CTG GTG AAC ACA ACA CACAGA CCA TTT GAC ATC 10429 Ser Asn Arg Gln Thr Leu Val Asn Thr Thr HisArg Pro Phe Asp Ile 3440 3445 3450 CAT GTG TAC CAT CCA TAT AGG CAG CCCATT GTG AGC AAT CCC TGT GGT 10477 His Val Tyr His Pro Tyr Arg Gln ProIle Val Ser Asn Pro Cys Gly 3455 3460 3465 3470 ACC AAC AAT GGT GGC TGTTCT CAT CTC TGC CTC ATC AAG CCA GGA GGA 10525 Thr Asn Asn Gly Gly CysSer His Leu Cys Leu Ile Lys Pro Gly Gly 3475 3480 3485 AAA GGG TTC ACTTGC GAG TGT CCA GAT GAC TTC CGC ACC CTT CAG CTG 10573 Lys Gly Phe ThrCys Glu Cys Pro Asp Asp Phe Arg Thr Leu Gln Leu 3490 3495 3500 AGT GGCAGC ACC TAC TGC ATG CCC ATG TGC TCC AGC ACC CAG TTC CTG 10621 Ser GlySer Thr Tyr Cys Met Pro Met Cys Ser Ser Thr Gln Phe Leu 3505 3510 3515TGC GCT AAC AAT GAA AAG TGC ATT CCT ATC TGG TGG AAA TGT GAT GGA 10669Cys Ala Asn Asn Glu Lys Cys Ile Pro Ile Trp Trp Lys Cys Asp Gly 35203525 3530 CAG AAA GAC TGC TCA GAT GGC TCT GAT GAA CTG GCC CTT TGC CCGCAG 10717 Gln Lys Asp Cys Ser Asp Gly Ser Asp Glu Leu Ala Leu Cys ProGln 3535 3540 3545 3550 CGC TTC TGC CGA CTG GGA CAG TTC CAG TGC AGT GACGGC AAC TGC ACC 10765 Arg Phe Cys Arg Leu Gly Gln Phe Gln Cys Ser AspGly Asn Cys Thr 3555 3560 3565 AGC CCG CAG ACT TTA TGC AAT GCT CAC CAAAAT TGC CCT GAT GGG TCT 10813 Ser Pro Gln Thr Leu Cys Asn Ala His GlnAsn Cys Pro Asp Gly Ser 3570 3575 3580 GAT GAA GAC CGT CTT CTT TGT GAGAAT CAC CAC TGT GAC TCC AAT GAA 10861 Asp Glu Asp Arg Leu Leu Cys GluAsn His His Cys Asp Ser Asn Glu 3585 3590 3595 TGG CAG TGC GCC AAC AAACGT TGC ATC CCA GAA TCC TGG CAG TGT GAC 10909 Trp Gln Cys Ala Asn LysArg Cys Ile Pro Glu Ser Trp Gln Cys Asp 3600 3605 3610 ACA TTT AAC GACTGT GAG GAT AAC TCA GAT GAA GAC AGT TCC CAC TGT 10957 Thr Phe Asn AspCys Glu Asp Asn Ser Asp Glu Asp Ser Ser His Cys 3615 3620 3625 3630 GCCAGC AGG ACC TGC CGG CCG GGC CAG TTT CGG TGT GCT AAT GGC CGC 11005 AlaSer Arg Thr Cys Arg Pro Gly Gln Phe Arg Cys Ala Asn Gly Arg 3635 36403645 TGC ATC CCG CAG GCC TGG AAG TGT GAT GTG GAT AAT GAT TGT GGA GAC11053 Cys Ile Pro Gln Ala Trp Lys Cys Asp Val Asp Asn Asp Cys Gly Asp3650 3655 3660 CAC TCG GAT GAG CCC ATT GAA GAA TGC ATG AGC TCT GCC CATCTC TGT 11101 His Ser Asp Glu Pro Ile Glu Glu Cys Met Ser Ser Ala HisLeu Cys 3665 3670 3675 GAC AAC TTC ACA GAA TTC AGC TGC AAA ACA AAT TACCGC TGC ATC CCA 11149 Asp Asn Phe Thr Glu Phe Ser Cys Lys Thr Asn TyrArg Cys Ile Pro 3680 3685 3690 AAG TGG GCC GTG TGC AAT GGT GTA GAT GACTGC AGG GAC AAC AGT GAT 11197 Lys Trp Ala Val Cys Asn Gly Val Asp AspCys Arg Asp Asn Ser Asp 3695 3700 3705 3710 GAG CAA GGC TGT GAG GAG AGGACA TGC CAT CCT GTG GGG GAT TTC CGC 11245 Glu Gln Gly Cys Glu Glu ArgThr Cys His Pro Val Gly Asp Phe Arg 3715 3720 3725 TGT AAA AAT CAC CACTGC ATC CCT CTT CGT TGG CAG TGT GAT GGG CAA 11293 Cys Lys Asn His HisCys Ile Pro Leu Arg Trp Gln Cys Asp Gly Gln 3730 3735 3740 AAT GAC TGTGGA GAT AAC TCA GAT GAG GAA AAC TGT GCT CCC CGG GAG 11341 Asn Asp CysGly Asp Asn Ser Asp Glu Glu Asn Cys Ala Pro Arg Glu 3745 3750 3755 TGCACA GAG AGC GAG TTT CGA TGT GTC AAT CAG CAG TGC ATT CCC TCG 11389 CysThr Glu Ser Glu Phe Arg Cys Val Asn Gln Gln Cys Ile Pro Ser 3760 37653770 CGA TGG ATC TGT GAC CAT TAC AAC GAC TGT GGG GAC AAC TCA GAT GAA11437 Arg Trp Ile Cys Asp His Tyr Asn Asp Cys Gly Asp Asn Ser Asp Glu3775 3780 3785 3790 CGG GAC TGT GAG ATG AGG ACC TGC CAT CCT GAA TAT TTTCAG TGT ACA 11485 Arg Asp Cys Glu Met Arg Thr Cys His Pro Glu Tyr PheGln Cys Thr 3795 3800 3805 AGT GGA CAT TGT GTA CAC AGT GAA CTG AAA TGCGAT GGA TCC GCT GAC 11533 Ser Gly His Cys Val His Ser Glu Leu Lys CysAsp Gly Ser Ala Asp 3810 3815 3820 TGT TTG GAT GCG TCT GAT GAA GCT GATTGT CCC ACA CGC TTT CCT GAT 11581 Cys Leu Asp Ala Ser Asp Glu Ala AspCys Pro Thr Arg Phe Pro Asp 3825 3830 3835 GGT GCA TAC TGC CAG GCT ACTATG TTC GAA TGC AAA AAC CAT GTT TGT 11629 Gly Ala Tyr Cys Gln Ala ThrMet Phe Glu Cys Lys Asn His Val Cys 3840 3845 3850 ATC CCG CCA TAT TGGAAA TGT GAT GGC GAT GAT GAC TGT GGC GAT GGT 11677 Ile Pro Pro Tyr TrpLys Cys Asp Gly Asp Asp Asp Cys Gly Asp Gly 3855 3860 3865 3870 TCA GATGAA GAA CTT CAC CTG TGC TTG GAT GTT CCC TGT AAT TCA CCA 11725 Ser AspGlu Glu Leu His Leu Cys Leu Asp Val Pro Cys Asn Ser Pro 3875 3880 3885AAC CGT TTC CGG TGT GAC AAC AAT CGC TGC ATT TAT AGT CAT GAG GTG 11773Asn Arg Phe Arg Cys Asp Asn Asn Arg Cys Ile Tyr Ser His Glu Val 38903895 3900 TGC AAT GGT GTG GAT GAC TGT GGA GAT GGA ACT GAT GAG ACA GAGGAG 11821 Cys Asn Gly Val Asp Asp Cys Gly Asp Gly Thr Asp Glu Thr GluGlu 3905 3910 3915 CAC TGT AGA AAA CCG ACC CCT AAA CCT TGT ACA GAA TATGAA TAT AAG 11869 His Cys Arg Lys Pro Thr Pro Lys Pro Cys Thr Glu TyrGlu Tyr Lys 3920 3925 3930 TGT GGC AAT GGG CAT TGC ATT CCA CAT GAC AATGTG TGT GAT GAT GCC 11917 Cys Gly Asn Gly His Cys Ile Pro His Asp AsnVal Cys Asp Asp Ala 3935 3940 3945 3950 GAT GAC TGT GGT GAC TGG TCC GATGAA CTG GGT TGC AAT AAA GGA AAA 11965 Asp Asp Cys Gly Asp Trp Ser AspGlu Leu Gly Cys Asn Lys Gly Lys 3955 3960 3965 GAA AGA ACA TGT GCT GAAAAT ATA TGC GAG CAA AAT TGT ACC CAA TTA 12013 Glu Arg Thr Cys Ala GluAsn Ile Cys Glu Gln Asn Cys Thr Gln Leu 3970 3975 3980 AAT GAA GGA GGATTT ATC TGC TCC TGT ACA GCT GGG TTC GAA ACC AAT 12061 Asn Glu Gly GlyPhe Ile Cys Ser Cys Thr Ala Gly Phe Glu Thr Asn 3985 3990 3995 GTT TTTGAC AGA ACC TCC TGT CTA GAT ATC AAT GAA TGT GAA CAA TTT 12109 Val PheAsp Arg Thr Ser Cys Leu Asp Ile Asn Glu Cys Glu Gln Phe 4000 4005 4010GGG ACT TGT CCC CAG CAC TGC AGA AAT ACC AAA GGA AGT TAT GAG TGT 12157Gly Thr Cys Pro Gln His Cys Arg Asn Thr Lys Gly Ser Tyr Glu Cys 40154020 4025 4030 GTC TGT GCT GAT GGC TTC ACG TCT ATG AGT GAC CGC CCT GGAAAA CGA 12205 Val Cys Ala Asp Gly Phe Thr Ser Met Ser Asp Arg Pro GlyLys Arg 4035 4040 4045 TGT GCA GCT GAG GGT AGC TCT CCT TTG TTG CTA CTGCCT GAC AAT GTC 12253 Cys Ala Ala Glu Gly Ser Ser Pro Leu Leu Leu LeuPro Asp Asn Val 4050 4055 4060 CGA ATT CGA AAA TAT AAT CTC TCA TCT GAGAGG TTC TCA GAG TAT CTT 12301 Arg Ile Arg Lys Tyr Asn Leu Ser Ser GluArg Phe Ser Glu Tyr Leu 4065 4070 4075 CAA GAT GAG GAA TAT ATC CAA GCTGTT GAT TAT GAT TGG GAT CCC RAG 12349 Gln Asp Glu Glu Tyr Ile Gln AlaVal Asp Tyr Asp Trp Asp Pro Xaa 4080 4085 4090 GAC ATA GGC CTC AGT GTTGTG TAT TAC ACT GTG CGA GGG GAG GGC TCT 12397 Asp Ile Gly Leu Ser ValVal Tyr Tyr Thr Val Arg Gly Glu Gly Ser 4095 4100 4105 4110 AGG TTT GGTGCT ATC AAA CGT GCC TAC ATC CCC AAC TTT GAA TCC GGC 12445 Arg Phe GlyAla Ile Lys Arg Ala Tyr Ile Pro Asn Phe Glu Ser Gly 4115 4120 4125 CGCAAT AAT CTT GTG CAG GAA GTT GAC CTG AAA CTG AAA TAC GTA ATG 12493 ArgAsn Asn Leu Val Gln Glu Val Asp Leu Lys Leu Lys Tyr Val Met 4130 41354140 CAG CCA GAT GGA ATA GCA GTG GAC TGG GTT GGA AGG CAT ATT TAC TGG12541 Gln Pro Asp Gly Ile Ala Val Asp Trp Val Gly Arg His Ile Tyr Trp4145 4150 4155 TCA GAT GTC AAG AAT AAA CGC ATT GAG GTG GCT AAA CTT GATGGA AGG 12589 Ser Asp Val Lys Asn Lys Arg Ile Glu Val Ala Lys Leu AspGly Arg 4160 4165 4170 TAC AGA AAG TGG CTG ATT TCC ACT GAC CTG GAC CAACCA GCT GCT ATT 12637 Tyr Arg Lys Trp Leu Ile Ser Thr Asp Leu Asp GlnPro Ala Ala Ile 4175 4180 4185 4190 GCT GTG AAT CCC AAA CTA GGG CTT ATGTTC TGG ACT GAC TGG GGA AAG 12685 Ala Val Asn Pro Lys Leu Gly Leu MetPhe Trp Thr Asp Trp Gly Lys 4195 4200 4205 GAA CCT AAA MTC GAG TCT GCCTGG ATG AAT GGA GAG GAC CGC AAC ATC 12733 Glu Pro Lys Xaa Glu Ser AlaTrp Met Asn Gly Glu Asp Arg Asn Ile 4210 4215 4220 CTG GTT TTC GAG GACCTT GGT TGG CCA ACT GGC CTT TCT ATC GAT TAT 12781 Leu Val Phe Glu AspLeu Gly Trp Pro Thr Gly Leu Ser Ile Asp Tyr 4225 4230 4235 TTG AAC AATGAC CGA ATC TAC TGG AGT GAC TTC AAG GAG GAC GTT ATT 12829 Leu Asn AsnAsp Arg Ile Tyr Trp Ser Asp Phe Lys Glu Asp Val Ile 4240 4245 4250 GAAACC ATA AAA TAT GAT GGG ACT GAT AGG AGA GTC ATT GCA AAG GAA 12877 GluThr Ile Lys Tyr Asp Gly Thr Asp Arg Arg Val Ile Ala Lys Glu 4255 42604265 4270 GCA ATG AAC CCT TAC AGC CTG GAC ATC TTT GAA GAC CAG TTA TACTGG 12925 Ala Met Asn Pro Tyr Ser Leu Asp Ile Phe Glu Asp Gln Leu TyrTrp 4275 4280 4285 ATA TCT AAG GAA AAG GGA GAA GTA TGG AAA CAA AAT AAATTT GGG CAA 12973 Ile Ser Lys Glu Lys Gly Glu Val Trp Lys Gln Asn LysPhe Gly Gln 4290 4295 4300 GGA AAG AAA GAG AAA ACG CTG GTA GTG AAC CCTTGG CTC ACT CAA GTT 13021 Gly Lys Lys Glu Lys Thr Leu Val Val Asn ProTrp Leu Thr Gln Val 4305 4310 4315 CGA ATC TTT CAT CAA CTC AGA TAC AATAAG TCA GTG CCC AAC CTT TGC 13069 Arg Ile Phe His Gln Leu Arg Tyr AsnLys Ser Val Pro Asn Leu Cys 4320 4325 4330 AAA CAG ATC TGC AGC CAC CTCTGC CTT CTG AGA CCT GGA GGA TAC AGC 13117 Lys Gln Ile Cys Ser His LeuCys Leu Leu Arg Pro Gly Gly Tyr Ser 4335 4340 4345 4350 TGT GCC TGT CCCCAA GGC TCC AGC TTT ATA GAG GGG AGC ACC ACT GAG 13165 Cys Ala Cys ProGln Gly Ser Ser Phe Ile Glu Gly Ser Thr Thr Glu 4355 4360 4365 TGT GATGCA GCC ATY GAA CTG CCT ATC AAC CTG CCC CCC CCA TGC AGG 13213 Cys AspAla Ala Ile Glu Leu Pro Ile Asn Leu Pro Pro Pro Cys Arg 4370 4375 4380TGC ATG CAC GGA GGA AAT TGC TAT TTT GAT GAG ACT GAC CTC CCC AAA 13261Cys Met His Gly Gly Asn Cys Tyr Phe Asp Glu Thr Asp Leu Pro Lys 43854390 4395 TGC AAG TGT CCT AGC GGC TAC ACC GGA AAA TAT TGT GAA ATG GCGTTT 13309 Cys Lys Cys Pro Ser Gly Tyr Thr Gly Lys Tyr Cys Glu Met AlaPhe 4400 4405 4410 TCA AAA GGC ATC TCT CCA GGA ACA ACC GCA GTA GCT GTGCTG TTG ACA 13357 Ser Lys Gly Ile Ser Pro Gly Thr Thr Ala Val Ala ValLeu Leu Thr 4415 4420 4425 4430 ATC CTC TTG ATC GTC GTA ATT GGA GCT CTGGCA ATT GCA GGA TTC TTC 13405 Ile Leu Leu Ile Val Val Ile Gly Ala LeuAla Ile Ala Gly Phe Phe 4435 4440 4445 CAC TAT AGA AGG ACC GGC TCC CTTTTG CCT GCT CTG CCC AAG CTG CCA 13453 His Tyr Arg Arg Thr Gly Ser LeuLeu Pro Ala Leu Pro Lys Leu Pro 4450 4455 4460 AGC TTA AGC AGT CTC GTCAAG CCC TCT GAA AAT GGG AAT GGG GTG ACC 13501 Ser Leu Ser Ser Leu ValLys Pro Ser Glu Asn Gly Asn Gly Val Thr 4465 4470 4475 TTC AGA TCA GGGGCA GAT CTT AAC ATG GAT ATT GGA GTG TCT GGT TTT 13549 Phe Arg Ser GlyAla Asp Leu Asn Met Asp Ile Gly Val Ser Gly Phe 4480 4485 4490 GGA CCTGAG ACT GCT ATT GAC AGG TCA ATG GCA ATG AGT GAA GAC TTT 13597 Gly ProGlu Thr Ala Ile Asp Arg Ser Met Ala Met Ser Glu Asp Phe 4495 4500 45054510 GTC ATG GAA ATG GGG AAG CAG CCC ATA ATA TTT GAA AAC CCA ATG TAC13645 Val Met Glu Met Gly Lys Gln Pro Ile Ile Phe Glu Asn Pro Met Tyr4515 4520 4525 TCA GCC AGA GAC AGT GCT GTC AAA GTG GTT CAG CCA ATC CAGGTG ACT 13693 Ser Ala Arg Asp Ser Ala Val Lys Val Val Gln Pro Ile GlnVal Thr 4530 4535 4540 GTA TCT GAA AAT GTG GAT AAT AAG AAT TAT GGA AGTCCC ATA AAC CCT 13741 Val Ser Glu Asn Val Asp Asn Lys Asn Tyr Gly SerPro Ile Asn Pro 4545 4550 4555 TCT GAG ATA GTT CCA GAG ACA AAC CCA ACTTCA CCA GCT GCT GAT GGA 13789 Ser Glu Ile Val Pro Glu Thr Asn Pro ThrSer Pro Ala Ala Asp Gly 4560 4565 4570 ACT CAG GTG ACA AAA TGG AAT CTCTTC AAA CGA AAA TCT AAA CAA ACT 13837 Thr Gln Val Thr Lys Trp Asn LeuPhe Lys Arg Lys Ser Lys Gln Thr 4575 4580 4585 4590 ACC AAC TTT GAA AATCCA ATC TAT GCA CAG ATG GAG AAC GAG CAA AAG 13885 Thr Asn Phe Glu AsnPro Ile Tyr Ala Gln Met Glu Asn Glu Gln Lys 4595 4600 4605 GAA AGT GTTGCT GCG ACA CCA CCT CCA TCA CCT TCG CTC CCT GCT AAG 13933 Glu Ser ValAla Ala Thr Pro Pro Pro Ser Pro Ser Leu Pro Ala Lys 4610 4615 4620 CCTAAG CCT CCT TCG AGA AGA GAC CCA ACT CCA ACC TAT TCT GCA ACA 13981 ProLys Pro Pro Ser Arg Arg Asp Pro Thr Pro Thr Tyr Ser Ala Thr 4625 46304635 GAA GAC ACT TTT AAA GAC ACC GCA AAT CTT GTT AAA GAA GAC TCT GAA14029 Glu Asp Thr Phe Lys Asp Thr Ala Asn Leu Val Lys Glu Asp Ser Glu4640 4645 4650 GTA TAG CTATACC 14042 Val * 4655 4655 amino acids aminoacid linear protein unknown 86 Met Asp Arg Gly Pro Ala Ala Val Ala CysThr Leu Leu Leu Ala Leu 1 5 10 15 Val Ala Cys Leu Ala Pro Ala Ser GlyGln Glu Cys Asp Ser Ala His 20 25 30 Phe Arg Cys Gly Ser Gly His Cys IlePro Ala Asp Trp Arg Cys Asp 35 40 45 Gly Thr Lys Asp Cys Ser Asp Asp AlaAsp Glu Ile Gly Cys Ala Val 50 55 60 Val Thr Cys Gln Gln Gly Tyr Phe LysCys Gln Ser Glu Gly Gln Cys 65 70 75 80 Ile Pro Ser Ser Trp Val Cys AspGln Asp Gln Asp Cys Asp Asp Gly 85 90 95 Ser Asp Glu Arg Gln Asp Cys SerGln Ser Thr Cys Ser Ser His Gln 100 105 110 Ile Thr Cys Ser Asn Gly GlnCys Ile Pro Ser Glu Tyr Arg Cys Asp 115 120 125 His Val Arg Asp Cys ProAsp Gly Ala Asp Glu Asn Asp Cys Gln Tyr 130 135 140 Pro Thr Cys Glu GlnLeu Thr Cys Asp Asn Gly Ala Cys Tyr Asn Thr 145 150 155 160 Ser Gln LysCys Asp Trp Lys Val Asp Cys Arg Asp Ser Ser Asp Glu 165 170 175 Ile AsnCys Thr Glu Ile Cys Leu His Asn Glu Phe Ser Cys Gly Asn 180 185 190 GlyGlu Cys Ile Pro Arg Ala Tyr Val Cys Asp His Asp Asn Asp Cys 195 200 205Gln Asp Gly Ser Asp Glu His Ala Cys Asn Tyr Pro Thr Cys Gly Gly 210 215220 Tyr Gln Phe Thr Cys Pro Ser Gly Arg Cys Ile Tyr Gln Asn Trp Val 225230 235 240 Cys Asp Gly Glu Asp Asp Cys Lys Asp Asn Gly Asp Glu Asp GlyCys 245 250 255 Glu Ser Gly Pro His Asp Val His Lys Cys Ser Pro Arg GluTrp Ser 260 265 270 Cys Pro Glu Ser Gly Arg Cys Ile Ser Ile Tyr Lys ValCys Asp Gly 275 280 285 Ile Leu Asp Cys Pro Gly Arg Glu Asp Glu Asn AsnThr Ser Thr Gly 290 295 300 Lys Tyr Cys Ser Met Thr Leu Cys Ser Ala LeuAsn Cys Gln Tyr Gln 305 310 315 320 Cys His Glu Thr Pro Tyr Gly Gly AlaCys Phe Cys Pro Pro Gly Tyr 325 330 335 Ile Ile Asn His Asn Asp Ser ArgThr Cys Val Glu Phe Asp Asp Cys 340 345 350 Gln Ile Trp Gly Ile Cys AspGln Lys Cys Glu Ser Arg Pro Gly Arg 355 360 365 His Leu Cys His Cys GluGlu Gly Tyr Ile Leu Glu Arg Gly Gln Tyr 370 375 380 Cys Lys Ala Asn AspSer Phe Gly Glu Ala Ser Ile Ile Phe Ser Asn 385 390 395 400 Gly Arg AspLeu Leu Ile Gly Asp Ile His Gly Arg Ser Phe Arg Ile 405 410 415 Leu ValGlu Ser Gln Asn Arg Gly Val Ala Val Gly Val Ala Phe His 420 425 430 TyrHis Leu Gln Arg Val Phe Trp Thr Asp Thr Val Gln Asn Lys Val 435 440 445Phe Ser Val Asp Ile Asn Gly Leu Asn Ile Gln Glu Val Leu Asn Val 450 455460 Ser Val Glu Thr Pro Glu Asn Leu Ala Val Asp Trp Val Asn Asn Lys 465470 475 480 Ile Tyr Leu Val Glu Thr Lys Val Asn Arg Ile Asp Met Val AsnLeu 485 490 495 Asp Gly Ser Tyr Arg Val Thr Leu Ile Thr Glu Asn Leu GlyHis Pro 500 505 510 Arg Gly Ile Ala Val Asp Pro Thr Val Gly Tyr Leu PhePhe Ser Asp 515 520 525 Trp Glu Ser Leu Ser Gly Glu Pro Lys Leu Glu ArgAla Phe Met Asp 530 535 540 Gly Ser Asn Arg Lys Asp Leu Val Lys Thr LysLeu Gly Trp Pro Ala 545 550 555 560 Gly Val Thr Leu Asp Met Ile Ser LysArg Val Tyr Trp Val Asp Ser 565 570 575 Arg Phe Asp Tyr Ile Glu Thr ValThr Tyr Asp Gly Ile Gln Arg Lys 580 585 590 Thr Val Val His Gly Gly SerLeu Ile Pro His Pro Phe Gly Val Ser 595 600 605 Leu Phe Glu Gly Gln ValPhe Phe Thr Asp Trp Thr Lys Met Ala Val 610 615 620 Leu Lys Ala Asn LysPhe Thr Glu Thr Asn Pro Gln Val Tyr Tyr Gln 625 630 635 640 Ala Ser LeuArg Pro Tyr Gly Val Thr Val Tyr His Ser Leu Arg Gln 645 650 655 Pro TyrAla Thr Asn Pro Cys Lys Asp Asn Asn Gly Gly Cys Glu Gln 660 665 670 ValCys Val Leu Ser His Arg Thr Asp Asn Asp Gly Leu Gly Phe Arg 675 680 685Cys Lys Cys Thr Phe Gly Phe Gln Leu Asp Thr Asp Glu Arg His Cys 690 695700 Ile Ala Val Gln Asn Phe Leu Ile Phe Ser Ser Gln Val Ala Ile Arg 705710 715 720 Gly Ile Pro Phe Thr Leu Ser Thr Gln Glu Asp Val Met Val ProVal 725 730 735 Ser Gly Asn Pro Ser Phe Phe Val Gly Ile Asp Phe Asp AlaGln Asp 740 745 750 Ser Thr Ile Phe Phe Ser Asp Met Ser Lys His Met IlePhe Lys Gln 755 760 765 Lys Ile Asp Gly Thr Gly Arg Glu Ile Leu Ala AlaAsn Arg Val Glu 770 775 780 Asn Val Glu Ser Leu Ala Phe Asp Trp Ile SerLys Asn Leu Tyr Trp 785 790 795 800 Thr Asp Ser His Tyr Lys Ser Ile SerVal Met Arg Leu Ala Asp Lys 805 810 815 Thr Arg Arg Thr Val Val Gln TyrLeu Asn Asn Pro Arg Ser Val Val 820 825 830 Val His Pro Phe Ala Gly TyrLeu Phe Phe Thr Asp Trp Phe Arg Pro 835 840 845 Ala Lys Ile Met Arg AlaTrp Ser Asp Gly Ser His Leu Leu Pro Val 850 855 860 Ile Asn Thr Thr LeuGly Trp Pro Asn Gly Leu Ala Ile Asp Trp Ala 865 870 875 880 Ala Ser ArgLeu Tyr Trp Val Asp Ala Tyr Phe Asp Lys Ile Glu His 885 890 895 Ser ThrPhe Asp Gly Leu Asp Arg Arg Arg Leu Gly His Ile Glu Gln 900 905 910 MetThr His Pro Phe Gly Leu Ala Ile Phe Gly Glu His Leu Phe Phe 915 920 925Thr Asp Trp Arg Leu Gly Ala Ile Ile Arg Val Arg Lys Ala Asp Gly 930 935940 Gly Glu Met Thr Val Ile Arg Ser Gly Ile Ala Tyr Ile Leu His Leu 945950 955 960 Lys Ser Tyr Asp Val Asn Ile Gln Thr Gly Ser Asn Ala Cys AsnGln 965 970 975 Pro Thr His Pro Asn Gly Asp Cys Ser His Phe Cys Phe ProVal Pro 980 985 990 Asn Phe Gln Arg Val Cys Gly Cys Pro Tyr Gly Met ArgLeu Ala Ser 995 1000 1005 Asn His Leu Thr Cys Glu Gly Asp Pro Thr AsnGlu Pro Pro Thr Glu 1010 1015 1020 Gln Cys Gly Leu Phe Ser Phe Pro CysLys Asn Gly Arg Cys Val Pro 1025 1030 1035 1040 Asn Tyr Tyr Leu Cys AspGly Val Asp Asp Cys His Asp Asn Ser Asp 1045 1050 1055 Glu Gln Leu CysGly Thr Leu Asn Asn Thr Cys Ser Ser Ser Ala Phe 1060 1065 1070 Thr CysGly His Gly Glu Cys Ile Pro Ala His Trp Arg Cys Asp Lys 1075 1080 1085Arg Asn Asp Cys Val Asp Gly Ser Asp Glu His Asn Cys Pro Thr His 10901095 1100 Ala Pro Ala Ser Cys Leu Asp Thr Gln Tyr Thr Cys Asp Asn HisGln 1105 1110 1115 1120 Cys Ile Ser Lys Asn Trp Val Cys Asp Thr Asp AsnAsp Cys Gly Asp 1125 1130 1135 Gly Ser Asp Glu Lys Asn Cys Asn Ser ThrGlu Thr Cys Gln Pro Ser 1140 1145 1150 Gln Phe Asn Cys Pro Asn His ArgCys Ile Asp Leu Ser Phe Val Cys 1155 1160 1165 Asp Gly Asp Lys Asp CysVal Asp Gly Ser Asp Glu Val Gly Cys Val 1170 1175 1180 Leu Asn Cys ThrAla Ser Gln Phe Lys Cys Ala Ser Gly Asp Lys Cys 1185 1190 1195 1200 IleGly Val Thr Asn Arg Cys Asp Gly Val Phe Asp Cys Ser Asp Asn 1205 12101215 Ser Asp Glu Ala Gly Cys Pro Thr Arg Pro Pro Gly Met Cys His Ser1220 1225 1230 Asp Glu Phe Gln Cys Gln Glu Asp Gly Ile Cys Ile Pro AsnPhe Trp 1235 1240 1245 Glu Cys Asp Gly His Pro Asp Cys Leu Tyr Gly SerAsp Glu His Asn 1250 1255 1260 Ala Cys Val Pro Lys Thr Cys Pro Ser SerTyr Phe His Cys Asp Asn 1265 1270 1275 1280 Gly Asn Cys Ile His Arg XaaTrp Leu Cys Asp Arg Asp Asn Asp Cys 1285 1290 1295 Gly Asp Met Ser AspGlu Lys Asp Cys Pro Thr Gln Pro Phe Arg Cys 1300 1305 1310 Pro Ser TrpGln Trp Gln Cys Leu Gly His Asn Ile Cys Val Asn Leu 1315 1320 1325 SerVal Val Cys Asp Gly Ile Phe Asp Cys Pro Asn Gly Thr Asp Glu 1330 13351340 Ser Pro Leu Cys Asn Gly Asn Ser Cys Ser Asp Phe Asn Gly Gly Cys1345 1350 1355 1360 Thr His Glu Cys Val Gln Glu Pro Phe Gly Ala Lys CysLeu Cys Pro 1365 1370 1375 Leu Gly Phe Leu Leu Ala Asn Asp Ser Lys ThrCys Glu Asp Ile Asp 1380 1385 1390 Glu Cys Asp Ile Leu Gly Ser Cys SerGln His Cys Tyr Asn Met Arg 1395 1400 1405 Gly Ser Phe Arg Cys Ser CysAsp Thr Gly Tyr Met Leu Glu Ser Asp 1410 1415 1420 Gly Arg Thr Cys LysVal Thr Ala Ser Glu Ser Leu Leu Leu Leu Val 1425 1430 1435 1440 Ala SerGln Asn Lys Ile Ile Ala Asp Ser Val Thr Ser Gln Val His 1445 1450 1455Asn Ile Tyr Ser Leu Val Glu Asn Gly Ser Tyr Ile Val Ala Val Asp 14601465 1470 Phe Asp Ser Ile Ser Gly Arg Ile Phe Trp Ser Asp Ala Thr GlnGly 1475 1480 1485 Lys Thr Trp Ser Ala Phe Gln Asn Gly Thr Asp Arg ArgVal Val Phe 1490 1495 1500 Asp Ser Ser Ile Ile Leu Thr Glu Thr Ile AlaIle Asp Trp Val Gly 1505 1510 1515 1520 Arg Asn Leu Tyr Trp Thr Asp TyrAla Leu Glu Thr Ile Glu Val Ser 1525 1530 1535 Lys Ile Asp Gly Ser HisArg Thr Val Leu Ile Ser Lys Asn Leu Thr 1540 1545 1550 Asn Pro Arg GlyLeu Ala Leu Asp Pro Arg Met Asn Glu His Leu Leu 1555 1560 1565 Phe TrpSer Asp Trp Gly His His Pro Arg Ile Glu Arg Ala Ser Met 1570 1575 1580Asp Gly Ser Met Arg Thr Val Ile Val Gln Asp Lys Ile Phe Trp Pro 15851590 1595 1600 Cys Gly Leu Thr Ile Asp Tyr Pro Asn Arg Leu Leu Tyr PheMet Asp 1605 1610 1615 Ser Tyr Leu Asp Tyr Met Asp Phe Cys Asp Tyr AsnGly His His Arg 1620 1625 1630 Arg Gln Val Ile Ala Ser Asp Leu Ile IleArg His Pro Tyr Ala Leu 1635 1640 1645 Thr Leu Phe Glu Asp Ser Val TyrTrp Thr Asp Arg Ala Thr Arg Arg 1650 1655 1660 Val Met Arg Ala Asn LysTrp His Gly Gly Asn Gln Ser Val Val Met 1665 1670 1675 1680 Tyr Asn IleGln Trp Pro Leu Gly Ile Val Ala Val His Pro Ser Lys 1685 1690 1695 GlnPro Asn Ser Val Asn Pro Cys Ala Phe Ser Arg Cys Ser His Leu 1700 17051710 Cys Leu Leu Ser Ser Gln Gly Pro His Phe Tyr Ser Cys Val Cys Pro1715 1720 1725 Ser Gly Trp Ser Leu Ser Pro Asp Leu Leu Asn Cys Leu ArgAsp Asp 1730 1735 1740 Gln Pro Phe Leu Ile Thr Val Arg Gln His Ile IlePhe Gly Ile Ser 1745 1750 1755 1760 Leu Asn Pro Glu Val Lys Ser Asn AspAla Met Val Pro Ile Ala Gly 1765 1770 1775 Ile Gln Asn Gly Leu Asp ValGlu Phe Asp Asp Ala Glu Gln Tyr Ile 1780 1785 1790 Tyr Trp Val Glu AsnPro Gly Glu Ile His Arg Val Lys Thr Asp Gly 1795 1800 1805 Thr Asn ArgThr Val Phe Ala Ser Ile Ser Met Val Gly Pro Ser Met 1810 1815 1820 AsnLeu Ala Leu Asp Trp Ile Ser Arg Asn Leu Tyr Ser Thr Asn Pro 1825 18301835 1840 Arg Thr Gln Ser Ile Glu Val Leu Thr Leu His Gly Asp Ile ArgTyr 1845 1850 1855 Arg Lys Thr Leu Ile Ala Asn Asp Gly Thr Ala Leu GlyVal Gly Phe 1860 1865 1870 Pro Ile Gly Ile Thr Val Asp Pro Ala Arg GlyLys Leu Tyr Trp Ser 1875 1880 1885 Asp Gln Gly Thr Asp Ser Gly Val ProAla Lys Ile Ala Ser Ala Asn 1890 1895 1900 Met Asp Gly Thr Ser Val LysThr Leu Phe Thr Gly Asn Leu Glu His 1905 1910 1915 1920 Leu Glu Cys ValThr Leu Asp Ile Glu Glu Gln Lys Leu Tyr Trp Ala 1925 1930 1935 Val ThrGly Arg Gly Val Ile Glu Arg Gly Asn Val Asp Gly Thr Asp 1940 1945 1950Arg Met Ile Leu Val His Gln Leu Ser His Pro Trp Gly Ile Ala Val 19551960 1965 His Asp Ser Phe Leu Tyr Tyr Thr Asp Glu Gln Tyr Glu Val IleGlu 1970 1975 1980 Arg Val Asp Lys Ala Thr Gly Ala Asn Lys Ile Val LeuArg Asp Asn 1985 1990 1995 2000 Val Pro Asn Leu Arg Gly Leu Gln Val TyrHis Arg Arg Asn Ala Ala 2005 2010 2015 Glu Ser Ser Asn Gly Cys Ser AsnAsn Met Asn Ala Cys Gln Gln Ile 2020 2025 2030 Cys Leu Pro Val Pro GlyGly Leu Phe Ser Cys Ala Cys Ala Thr Gly 2035 2040 2045 Phe Lys Leu AsnPro Asp Asn Arg Ser Cys Ser Pro Tyr Asn Ser Phe 2050 2055 2060 Ile ValVal Ser Met Leu Ser Ala Ile Arg Gly Phe Ser Leu Glu Leu 2065 2070 20752080 Ser Asp His Ser Glu Thr Met Val Pro Val Ala Gly Gln Gly Arg Asn2085 2090 2095 Ala Leu His Val Asp Val Asp Val Ser Ser Gly Phe Ile TyrTrp Cys 2100 2105 2110 Asp Phe Ser Ser Ser Val Ala Ser Asp Asn Ala IleArg Arg Ile Lys 2115 2120 2125 Pro Asp Gly Ser Ser Leu Met Asn Ile ValThr His Gly Ile Gly Glu 2130 2135 2140 Asn Gly Val Arg Gly Ile Ala ValAsp Trp Val Ala Gly Asn Leu Tyr 2145 2150 2155 2160 Phe Thr Asn Ala PheVal Ser Glu Thr Leu Ile Glu Val Leu Arg Ile 2165 2170 2175 Asn Thr ThrTyr Arg Arg Val Leu Leu Lys Val Thr Val Asp Met Pro 2180 2185 2190 ArgHis Ile Val Val Asp Pro Lys Asn Arg Tyr Leu Phe Trp Ala Asp 2195 22002205 Tyr Gly Gln Arg Pro Lys Ile Glu Arg Ser Phe Leu Asp Cys Thr Asn2210 2215 2220 Arg Thr Val Leu Val Ser Glu Gly Ile Val Thr Pro Arg GlyLeu Ala 2225 2230 2235 2240 Val Asp Arg Ser Asp Gly Tyr Val Tyr Trp ValAsp Asp Ser Leu Asp 2245 2250 2255 Ile Ile Ala Arg Ile Arg Ile Asn GlyGlu Asn Ser Glu Val Ile Arg 2260 2265 2270 Tyr Gly Ser Arg Tyr Pro ThrPro Tyr Gly Ile Thr Val Phe Glu Asn 2275 2280 2285 Ser Ile Ile Trp ValAsp Arg Asn Leu Lys Lys Ile Phe Gln Ala Ser 2290 2295 2300 Lys Glu ProGlu Asn Thr Glu Pro Pro Thr Val Ile Arg Asp Asn Ile 2305 2310 2315 2320Asn Trp Leu Arg Asp Val Thr Ile Phe Asp Lys Gln Val Gln Pro Arg 23252330 2335 Ser Pro Ala Glu Val Asn Asn Asn Pro Cys Leu Glu Asn Asn GlyGly 2340 2345 2350 Cys Ser His Leu Cys Phe Ala Leu Pro Gly Leu His ThrPro Lys Cys 2355 2360 2365 Asp Cys Ala Phe Gly Thr Leu Gln Ser Asp GlyLys Asn Cys Ala Ile 2370 2375 2380 Ser Thr Glu Asn Phe Leu Ile Phe AlaLeu Ser Asn Ser Leu Arg Ser 2385 2390 2395 2400 Leu His Leu Asp Pro GluAsn His Ser Pro Pro Phe Gln Thr Ile Asn 2405 2410 2415 Val Glu Arg ThrVal Met Ser Leu Asp Tyr Asp Ser Val Ser Asp Arg 2420 2425 2430 Ile TyrPhe Thr Gln Asn Leu Ala Ser Gly Val Gly Gln Ile Ser Tyr 2435 2440 2445Ala Thr Leu Ser Ser Gly Ile His Thr Pro Thr Val Ile Ala Ser Gly 24502455 2460 Ile Gly Thr Ala Asp Gly Ile Ala Phe Asp Trp Ile Thr Arg ArgIle 2465 2470 2475 2480 Tyr Tyr Ser Asp Tyr Leu Asn Gln Met Ile Asn SerMet Ala Glu Asp 2485 2490 2495 Gly Ser Asn Arg Thr Val Ile Ala Arg ValPro Lys Pro Arg Ala Ile 2500 2505 2510 Val Leu Asp Pro Cys Gln Gly TyrLeu Tyr Trp Ala Asp Trp Asp Thr 2515 2520 2525 His Ala Lys Ile Glu ArgAla Thr Leu Gly Gly Asn Phe Arg Val Pro 2530 2535 2540 Ile Val Asn SerSer Leu Val Met Pro Ser Gly Leu Thr Leu Asp Tyr 2545 2550 2555 2560 GluGlu Asp Leu Leu Tyr Trp Val Asp Ala Ser Leu Gln Arg Ile Glu 2565 25702575 Arg Ser Thr Leu Thr Gly Val Asp Arg Glu Val Ile Val Asn Ala Ala2580 2585 2590 Val His Ala Phe Gly Leu Thr Leu Tyr Gly Gln Tyr Ile TyrTrp Thr 2595 2600 2605 Asp Leu Tyr Thr Gln Arg Ile Tyr Arg Ala Asn LysTyr Asp Gly Ser 2610 2615 2620 Gly Gln Ile Ala Met Thr Thr Asn Leu LeuSer Gln Pro Arg Gly Ile 2625 2630 2635 2640 Asn Thr Val Val Lys Asn GlnLys Gln Gln Cys Asn Asn Pro Cys Glu 2645 2650 2655 Gln Phe Asn Gly GlyCys Ser His Ile Cys Ala Pro Gly Pro Asn Gly 2660 2665 2670 Ala Glu CysGln Cys Pro His Glu Gly Asn Trp Tyr Leu Ala Asn Asn 2675 2680 2685 ArgLys His Cys Ile Val Asp Asn Gly Glu Arg Cys Gly Ala Ser Ser 2690 26952700 Phe Thr Cys Ser Asn Gly Arg Cys Ile Ser Glu Glu Trp Lys Cys Asp2705 2710 2715 2720 Asn Asp Asn Asp Cys Gly Asp Gly Ser Asp Glu Met GluSer Val Cys 2725 2730 2735 Ala Leu His Thr Cys Ser Pro Thr Ala Phe ThrCys Ala Asn Gly Arg 2740 2745 2750 Cys Val Gln Tyr Ser Tyr Arg Cys AspTyr Tyr Asn Asp Cys Gly Asp 2755 2760 2765 Gly Ser Asp Glu Ala Gly CysLeu Phe Arg Asp Cys Asn Ala Thr Thr 2770 2775 2780 Glu Phe Met Cys AsnAsn Arg Arg Cys Ile Pro Arg Glu Phe Ile Cys 2785 2790 2795 2800 Asn GlyVal Asp Asn Cys His Asp Asn Asn Thr Ser Asp Glu Lys Asn 2805 2810 2815Cys Pro Asp Arg Thr Cys Gln Ser Gly Tyr Thr Lys Cys His Asn Ser 28202825 2830 Asn Ile Cys Ile Pro Arg Val Tyr Leu Cys Asp Gly Asp Asn AspCys 2835 2840 2845 Gly Asp Asn Ser Asp Glu Asn Pro Thr Tyr Cys Thr ThrHis Thr Cys 2850 2855 2860 Ser Ser Ser Glu Phe Gln Cys Thr Ser Gly ArgCys Ile Pro Gln His 2865 2870 2875 2880 Trp Tyr Cys Asp Gln Glu Thr AspCys Phe Asp Ala Ser Asp Glu Pro 2885 2890 2895 Ala Ser Cys Gly His SerGlu Arg Thr Cys Leu Ala Asp Glu Phe Lys 2900 2905 2910 Cys Asp Gly GlyArg Cys Ile Pro Ser Glu Trp Ile Cys Asp Gly Asp 2915 2920 2925 Asn AspCys Gly Asp Met Ser Asp Glu Asp Lys Arg His Gln Cys Gln 2930 2935 2940Asn Gln Asn Cys Ser Asp Ser Glu Phe Leu Cys Val Asn Asp Arg Pro 29452950 2955 2960 Pro Asp Arg Arg Cys Ile Pro Gln Ser Trp Val Cys Asp GlyAsp Val 2965 2970 2975 Asp Cys Thr Asp Gly Tyr Asp Glu Asn Gln Asn CysThr Arg Arg Thr 2980 2985 2990 Cys Ser Glu Asn Glu Phe Thr Cys Gly TyrGly Leu Cys Ile Pro Lys 2995 3000 3005 Ile Phe Arg Cys Asp Arg His AsnAsp Cys Gly Asp Tyr Ser Asp Glu 3010 3015 3020 Arg Gly Cys Leu Tyr GlnThr Cys Gln Gln Asn Gln Phe Thr Cys Gln 3025 3030 3035 3040 Asn Gly ArgCys Ile Ser Lys Thr Phe Val Cys Asp Glu Asp Asn Asp 3045 3050 3055 CysGly Asp Gly Ser Asp Glu Leu Met His Leu Cys His Thr Pro Glu 3060 30653070 Pro Thr Cys Pro Pro His Glu Phe Lys Cys Asp Asn Gly Arg Cys Ile3075 3080 3085 Glu Met Met Lys Leu Cys Asn His Leu Asp Asp Cys Leu AspAsn Ser 3090 3095 3100 Asp Glu Lys Gly Cys Gly Ile Asn Glu Cys His AspPro Ser Ile Ser 3105 3110 3115 3120 Gly Cys Asp His Asn Cys Thr Asp ThrLeu Thr Ser Phe Tyr Cys Ser 3125 3130 3135 Cys Arg Pro Gly Tyr Lys LeuMet Ser Asp Lys Arg Thr Cys Val Asp 3140 3145 3150 Ile Asp Glu Cys ThrGlu Met Pro Phe Val Cys Ser Gln Lys Cys Glu 3155 3160 3165 Asn Val IleGly Ser Tyr Ile Cys Lys Cys Ala Pro Gly Tyr Leu Arg 3170 3175 3180 GluPro Asp Gly Lys Thr Cys Arg Gln Asn Ser Asn Ile Glu Pro Tyr 3185 31903195 3200 Leu Ile Phe Ser Asn Arg Tyr Tyr Leu Arg Asn Leu Thr Ile AspGly 3205 3210 3215 Tyr Phe Tyr Ser Leu Ile Leu Glu Gly Leu Asp Asn ValVal Ala Leu 3220 3225 3230 Asp Phe Asp Arg Val Glu Lys Arg Leu Tyr TrpIle Asp Thr Gln Arg 3235 3240 3245 Gln Val Ile Glu Arg Met Phe Leu AsnLys Thr Asn Lys Glu Thr Ile 3250 3255 3260 Ile Asn His Arg Leu Pro AlaAla Glu Ser Leu Ala Val Asp Trp Val 3265 3270 3275 3280 Ser Arg Lys LeuTyr Trp Leu Asp Ala Arg Leu Asp Gly Leu Phe Val 3285 3290 3295 Ser AspLeu Asn Gly Gly His Arg Arg Met Leu Ala Gln His Cys Val 3300 3305 3310Asp Ala Asn Asn Thr Phe Cys Phe Asp Asn Pro Arg Gly Leu Ala Leu 33153320 3325 His Pro Gln Tyr Gly Tyr Leu Tyr Trp Ala Asp Trp Gly His ArgAla 3330 3335 3340 Tyr Ile Gly Arg Val Gly Met Asp Gly Thr Asn Lys SerVal Ile Ile 3345 3350 3355 3360 Ser Thr Lys Leu Glu Trp Pro Asn Gly IleThr Ile Asp Tyr Thr Asn 3365 3370 3375 Asp Leu Leu Tyr Trp Ala Asp AlaHis Leu Gly Tyr Ile Glu Tyr Ser 3380 3385 3390 Asp Leu Glu Gly His HisArg His Thr Val Tyr Asp Gly Ala Leu Pro 3395 3400 3405 His Pro Phe AlaIle Thr Ile Phe Glu Asp Thr Ile Tyr Trp Thr Asp 3410 3415 3420 Trp AsnThr Arg Thr Val Glu Lys Gly Asn Lys Tyr Asp Gly Ser Asn 3425 3430 34353440 Arg Gln Thr Leu Val Asn Thr Thr His Arg Pro Phe Asp Ile His Val3445 3450 3455 Tyr His Pro Tyr Arg Gln Pro Ile Val Ser Asn Pro Cys GlyThr Asn 3460 3465 3470 Asn Gly Gly Cys Ser His Leu Cys Leu Ile Lys ProGly Gly Lys Gly 3475 3480 3485 Phe Thr Cys Glu Cys Pro Asp Asp Phe ArgThr Leu Gln Leu Ser Gly 3490 3495 3500 Ser Thr Tyr Cys Met Pro Met CysSer Ser Thr Gln Phe Leu Cys Ala 3505 3510 3515 3520 Asn Asn Glu Lys CysIle Pro Ile Trp Trp Lys Cys Asp Gly Gln Lys 3525 3530 3535 Asp Cys SerAsp Gly Ser Asp Glu Leu Ala Leu Cys Pro Gln Arg Phe 3540 3545 3550 CysArg Leu Gly Gln Phe Gln Cys Ser Asp Gly Asn Cys Thr Ser Pro 3555 35603565 Gln Thr Leu Cys Asn Ala His Gln Asn Cys Pro Asp Gly Ser Asp Glu3570 3575 3580 Asp Arg Leu Leu Cys Glu Asn His His Cys Asp Ser Asn GluTrp Gln 3585 3590 3595 3600 Cys Ala Asn Lys Arg Cys Ile Pro Glu Ser TrpGln Cys Asp Thr Phe 3605 3610 3615 Asn Asp Cys Glu Asp Asn Ser Asp GluAsp Ser Ser His Cys Ala Ser 3620 3625 3630 Arg Thr Cys Arg Pro Gly GlnPhe Arg Cys Ala Asn Gly Arg Cys Ile 3635 3640 3645 Pro Gln Ala Trp LysCys Asp Val Asp Asn Asp Cys Gly Asp His Ser 3650 3655 3660 Asp Glu ProIle Glu Glu Cys Met Ser Ser Ala His Leu Cys Asp Asn 3665 3670 3675 3680Phe Thr Glu Phe Ser Cys Lys Thr Asn Tyr Arg Cys Ile Pro Lys Trp 36853690 3695 Ala Val Cys Asn Gly Val Asp Asp Cys Arg Asp Asn Ser Asp GluGln 3700 3705 3710 Gly Cys Glu Glu Arg Thr Cys His Pro Val Gly Asp PheArg Cys Lys 3715 3720 3725 Asn His His Cys Ile Pro Leu Arg Trp Gln CysAsp Gly Gln Asn Asp 3730 3735 3740 Cys Gly Asp Asn Ser Asp Glu Glu AsnCys Ala Pro Arg Glu Cys Thr 3745 3750 3755 3760 Glu Ser Glu Phe Arg CysVal Asn Gln Gln Cys Ile Pro Ser Arg Trp 3765 3770 3775 Ile Cys Asp HisTyr Asn Asp Cys Gly Asp Asn Ser Asp Glu Arg Asp 3780 3785 3790 Cys GluMet Arg Thr Cys His Pro Glu Tyr Phe Gln Cys Thr Ser Gly 3795 3800 3805His Cys Val His Ser Glu Leu Lys Cys Asp Gly Ser Ala Asp Cys Leu 38103815 3820 Asp Ala Ser Asp Glu Ala Asp Cys Pro Thr Arg Phe Pro Asp GlyAla 3825 3830 3835 3840 Tyr Cys Gln Ala Thr Met Phe Glu Cys Lys Asn HisVal Cys Ile Pro 3845 3850 3855 Pro Tyr Trp Lys Cys Asp Gly Asp Asp AspCys Gly Asp Gly Ser Asp 3860 3865 3870 Glu Glu Leu His Leu Cys Leu AspVal Pro Cys Asn Ser Pro Asn Arg 3875 3880 3885 Phe Arg Cys Asp Asn AsnArg Cys Ile Tyr Ser His Glu Val Cys Asn 3890 3895 3900 Gly Val Asp AspCys Gly Asp Gly Thr Asp Glu Thr Glu Glu His Cys 3905 3910 3915 3920 ArgLys Pro Thr Pro Lys Pro Cys Thr Glu Tyr Glu Tyr Lys Cys Gly 3925 39303935 Asn Gly His Cys Ile Pro His Asp Asn Val Cys Asp Asp Ala Asp Asp3940 3945 3950 Cys Gly Asp Trp Ser Asp Glu Leu Gly Cys Asn Lys Gly LysGlu Arg 3955 3960 3965 Thr Cys Ala Glu Asn Ile Cys Glu Gln Asn Cys ThrGln Leu Asn Glu 3970 3975 3980 Gly Gly Phe Ile Cys Ser Cys Thr Ala GlyPhe Glu Thr Asn Val Phe 3985 3990 3995 4000 Asp Arg Thr Ser Cys Leu AspIle Asn Glu Cys Glu Gln Phe Gly Thr 4005 4010 4015 Cys Pro Gln His CysArg Asn Thr Lys Gly Ser Tyr Glu Cys Val Cys 4020 4025 4030 Ala Asp GlyPhe Thr Ser Met Ser Asp Arg Pro Gly Lys Arg Cys Ala 4035 4040 4045 AlaGlu Gly Ser Ser Pro Leu Leu Leu Leu Pro Asp Asn Val Arg Ile 4050 40554060 Arg Lys Tyr Asn Leu Ser Ser Glu Arg Phe Ser Glu Tyr Leu Gln Asp4065 4070 4075 4080 Glu Glu Tyr Ile Gln Ala Val Asp Tyr Asp Trp Asp ProXaa Asp Ile 4085 4090 4095 Gly Leu Ser Val Val Tyr Tyr Thr Val Arg GlyGlu Gly Ser Arg Phe 4100 4105 4110 Gly Ala Ile Lys Arg Ala Tyr Ile ProAsn Phe Glu Ser Gly Arg Asn 4115 4120 4125 Asn Leu Val Gln Glu Val AspLeu Lys Leu Lys Tyr Val Met Gln Pro 4130 4135 4140 Asp Gly Ile Ala ValAsp Trp Val Gly Arg His Ile Tyr Trp Ser Asp 4145 4150 4155 4160 Val LysAsn Lys Arg Ile Glu Val Ala Lys Leu Asp Gly Arg Tyr Arg 4165 4170 4175Lys Trp Leu Ile Ser Thr Asp Leu Asp Gln Pro Ala Ala Ile Ala Val 41804185 4190 Asn Pro Lys Leu Gly Leu Met Phe Trp Thr Asp Trp Gly Lys GluPro 4195 4200 4205 Lys Xaa Glu Ser Ala Trp Met Asn Gly Glu Asp Arg AsnIle Leu Val 4210 4215 4220 Phe Glu Asp Leu Gly Trp Pro Thr Gly Leu SerIle Asp Tyr Leu Asn 4225 4230 4235 4240 Asn Asp Arg Ile Tyr Trp Ser AspPhe Lys Glu Asp Val Ile Glu Thr 4245 4250 4255 Ile Lys Tyr Asp Gly ThrAsp Arg Arg Val Ile Ala Lys Glu Ala Met 4260 4265 4270 Asn Pro Tyr SerLeu Asp Ile Phe Glu Asp Gln Leu Tyr Trp Ile Ser 4275 4280 4285 Lys GluLys Gly Glu Val Trp Lys Gln Asn Lys Phe Gly Gln Gly Lys 4290 4295 4300Lys Glu Lys Thr Leu Val Val Asn Pro Trp Leu Thr Gln Val Arg Ile 43054310 4315 4320 Phe His Gln Leu Arg Tyr Asn Lys Ser Val Pro Asn Leu CysLys Gln 4325 4330 4335 Ile Cys Ser His Leu Cys Leu Leu Arg Pro Gly GlyTyr Ser Cys Ala 4340 4345 4350 Cys Pro Gln Gly Ser Ser Phe Ile Glu GlySer Thr Thr Glu Cys Asp 4355 4360 4365 Ala Ala Ile Glu Leu Pro Ile AsnLeu Pro Pro Pro Cys Arg Cys Met 4370 4375 4380 His Gly Gly Asn Cys TyrPhe Asp Glu Thr Asp Leu Pro Lys Cys Lys 4385 4390 4395 4400 Cys Pro SerGly Tyr Thr Gly Lys Tyr Cys Glu Met Ala Phe Ser Lys 4405 4410 4415 GlyIle Ser Pro Gly Thr Thr Ala Val Ala Val Leu Leu Thr Ile Leu 4420 44254430 Leu Ile Val Val Ile Gly Ala Leu Ala Ile Ala Gly Phe Phe His Tyr4435 4440 4445 Arg Arg Thr Gly Ser Leu Leu Pro Ala Leu Pro Lys Leu ProSer Leu 4450 4455 4460 Ser Ser Leu Val Lys Pro Ser Glu Asn Gly Asn GlyVal Thr Phe Arg 4465 4470 4475 4480 Ser Gly Ala Asp Leu Asn Met Asp IleGly Val Ser Gly Phe Gly Pro 4485 4490 4495 Glu Thr Ala Ile Asp Arg SerMet Ala Met Ser Glu Asp Phe Val Met 4500 4505 4510 Glu Met Gly Lys GlnPro Ile Ile Phe Glu Asn Pro Met Tyr Ser Ala 4515 4520 4525 Arg Asp SerAla Val Lys Val Val Gln Pro Ile Gln Val Thr Val Ser 4530 4535 4540 GluAsn Val Asp Asn Lys Asn Tyr Gly Ser Pro Ile Asn Pro Ser Glu 4545 45504555 4560 Ile Val Pro Glu Thr Asn Pro Thr Ser Pro Ala Ala Asp Gly ThrGln 4565 4570 4575 Val Thr Lys Trp Asn Leu Phe Lys Arg Lys Ser Lys GlnThr Thr Asn 4580 4585 4590 Phe Glu Asn Pro Ile Tyr Ala Gln Met Glu AsnGlu Gln Lys Glu Ser 4595 4600 4605 Val Ala Ala Thr Pro Pro Pro Ser ProSer Leu Pro Ala Lys Pro Lys 4610 4615 4620 Pro Pro Ser Arg Arg Asp ProThr Pro Thr Tyr Ser Ala Thr Glu Asp 4625 4630 4635 4640 Thr Phe Lys AspThr Ala Asn Leu Val Lys Glu Asp Ser Glu Val 4645 4650 4655 14080 basepairs nucleic acid single linear cDNA NO NO Homo sapiens Kidney CDS105..14072 87 GCAGACCTAA AGGAGCGTTC GCTAGCAGAG GCGCTGCCGG TGCGGTGTGCTACGCGCGCC 60 CACCTCCCGG GGAAGGAACG GCGAGGCCGG GGACCGTCGC GGAG ATG GATCGC GGG 116 Met Asp Arg Gly 4660 CCG GCA GCA GTG GCG TGC ACG CTG CTC CTGGCT CTC GTC GCC TGC CTA 164 Pro Ala Ala Val Ala Cys Thr Leu Leu Leu AlaLeu Val Ala Cys Leu 4665 4670 4675 GCG CCG GCC AGT GGC CAA GAA TGT GACAGT GCG CAT TTT CGC TGT GGA 212 Ala Pro Ala Ser Gly Gln Glu Cys Asp SerAla His Phe Arg Cys Gly 4680 4685 4690 AGT GGG CAT TGC ATC CCT GCA GACTGG AGG TGT GAT GGG ACC AAA GAC 260 Ser Gly His Cys Ile Pro Ala Asp TrpArg Cys Asp Gly Thr Lys Asp 4695 4700 4705 TGT TCA GAT GAC GCG GAT GAAATT GGC TGC GCT GTT GTG ACC TGC CAG 308 Cys Ser Asp Asp Ala Asp Glu IleGly Cys Ala Val Val Thr Cys Gln 4710 4715 4720 CAG GGC TAT TTC AAG TGCCAG AGT GAG GGA CAA TGC ATC CCC AGC TCC 356 Gln Gly Tyr Phe Lys Cys GlnSer Glu Gly Gln Cys Ile Pro Ser Ser 4725 4730 4735 4740 TGG GTG TGT GACCAA GAT CAA GAC TGT GAT GAT GGC TCA GAT GAA CGT 404 Trp Val Cys Asp GlnAsp Gln Asp Cys Asp Asp Gly Ser Asp Glu Arg 4745 4750 4755 CAA GAT TGCTCA CAA AGT ACA TGC TCA AGT CAT CAG ATA ACA TGC TCC 452 Gln Asp Cys SerGln Ser Thr Cys Ser Ser His Gln Ile Thr Cys Ser 4760 4765 4770 AAT GGTCAG TGT ATC CCA AGT GAA TAC AGG TGC GAC CAC GTC AGA GAC 500 Asn Gly GlnCys Ile Pro Ser Glu Tyr Arg Cys Asp His Val Arg Asp 4775 4780 4785 TGCCCC GAT GGA GCT GAT GAG AAT GAC TGC CAG TAC CCA ACA TGT GAG 548 Cys ProAsp Gly Ala Asp Glu Asn Asp Cys Gln Tyr Pro Thr Cys Glu 4790 4795 4800CAG CTT ACT TGT GAC AAT GGG GCC TGC TAT AAC ACC AGT CAG AAG TGT 596 GlnLeu Thr Cys Asp Asn Gly Ala Cys Tyr Asn Thr Ser Gln Lys Cys 4805 48104815 4820 GAT TGG AAA GTT GAT TGC AGG GAC TCC TCA GAT GAA ATC AAC TGCACT 644 Asp Trp Lys Val Asp Cys Arg Asp Ser Ser Asp Glu Ile Asn Cys Thr4825 4830 4835 GAG ATA TGC TTG CAC AAT GAG TTT TCA TGT GGC AAT GGA GAGTGT ATC 692 Glu Ile Cys Leu His Asn Glu Phe Ser Cys Gly Asn Gly Glu CysIle 4840 4845 4850 CCT CGT GCT TAT GTC TGT GAC CAT GAC AAT GAT TGC CAAGAC GGC AGT 740 Pro Arg Ala Tyr Val Cys Asp His Asp Asn Asp Cys Gln AspGly Ser 4855 4860 4865 GAT GAA CAT GCT TGC AAC TAT CCG ACC TGC GGT GGTTAC CAG TTC ACT 788 Asp Glu His Ala Cys Asn Tyr Pro Thr Cys Gly Gly TyrGln Phe Thr 4870 4875 4880 TGC CCC AGT GGC CGA TGC ATT TAT CAA AAC TGGGTT TGT GAT GGA GAA 836 Cys Pro Ser Gly Arg Cys Ile Tyr Gln Asn Trp ValCys Asp Gly Glu 4885 4890 4895 4900 GAT GAC TGT AAA GAT AAT GGA GAT GAAGAT GGA TGT GAA AGC GGT CCT 884 Asp Asp Cys Lys Asp Asn Gly Asp Glu AspGly Cys Glu Ser Gly Pro 4905 4910 4915 CAT GAT GTT CAT AAA TGT TCC CCAAGA GAA TGG TCT TGC CCA GAG TCG 932 His Asp Val His Lys Cys Ser Pro ArgGlu Trp Ser Cys Pro Glu Ser 4920 4925 4930 GGA CGA TGC ATC TCC ATT TATAAA GTT TGT GAT GGG ATT TTA GAT TGC 980 Gly Arg Cys Ile Ser Ile Tyr LysVal Cys Asp Gly Ile Leu Asp Cys 4935 4940 4945 CCA GGA AGA GAA GAT GAAAAC AAC ACT AGT ACC GGA AAA TAC TGT AGT 1028 Pro Gly Arg Glu Asp Glu AsnAsn Thr Ser Thr Gly Lys Tyr Cys Ser 4950 4955 4960 ATG ACT CTG TGC TCTGCC TTG AAC TGC CAG TAC CAG TGC CAT GAG ACG 1076 Met Thr Leu Cys Ser AlaLeu Asn Cys Gln Tyr Gln Cys His Glu Thr 4965 4970 4975 4980 CCG TAT GGAGGA GCG TGT TTT TGT CCC CCA GGT TAT ATC ATC AAC CAC 1124 Pro Tyr Gly GlyAla Cys Phe Cys Pro Pro Gly Tyr Ile Ile Asn His 4985 4990 4995 AAT GACAGC CGT ACC TGT GTT GAG TTT GAT GAT TGC CAG ATA TGG GGA 1172 Asn Asp SerArg Thr Cys Val Glu Phe Asp Asp Cys Gln Ile Trp Gly 5000 5005 5010 ATTTGT GAC CAG AAG TGT GAA AGC CGA CCT GGC CGT CAC CTG TGC CAC 1220 Ile CysAsp Gln Lys Cys Glu Ser Arg Pro Gly Arg His Leu Cys His 5015 5020 5025TGT GAA GAA GGG TAT ATC TTG GAG CGT GGA CAG TAT TGC AAA GCT AAT 1268 CysGlu Glu Gly Tyr Ile Leu Glu Arg Gly Gln Tyr Cys Lys Ala Asn 5030 50355040 GAT TCC TTT GGC GAG GCC TCC ATT ATC TTC TCC AAT GGT CGG GAT TTG1316 Asp Ser Phe Gly Glu Ala Ser Ile Ile Phe Ser Asn Gly Arg Asp Leu5045 5050 5055 5060 TTA ATT GGT GAT ATT CAT GGA AGG AGC TTC CGG ATC CTAGTG GAG TCT 1364 Leu Ile Gly Asp Ile His Gly Arg Ser Phe Arg Ile Leu ValGlu Ser 5065 5070 5075 CAG AAT CGT GGA GTG GCC GTG GGT GTG GCT TTC CACTAT CAC CTG CAA 1412 Gln Asn Arg Gly Val Ala Val Gly Val Ala Phe His TyrHis Leu Gln 5080 5085 5090 AGA GTT TTT TGG ACA GAC ACC GTG CAA AAT AAGGTT TTT TCA GTT GAC 1460 Arg Val Phe Trp Thr Asp Thr Val Gln Asn Lys ValPhe Ser Val Asp 5095 5100 5105 ATT AAT GGT TTA AAT ATC CAA GAG GTT CTCAAT GTT TCT GTT GAA ACC 1508 Ile Asn Gly Leu Asn Ile Gln Glu Val Leu AsnVal Ser Val Glu Thr 5110 5115 5120 CCA GAG AAC CTG GCT GTG GAC TGG GTTAAT AAT AAA ATC TAT CTA GTG 1556 Pro Glu Asn Leu Ala Val Asp Trp Val AsnAsn Lys Ile Tyr Leu Val 5125 5130 5135 5140 GAA ACC AAG GTC AAC CGC ATAGAT ATG GTA AAT TTG GAT GGA AGC TAT 1604 Glu Thr Lys Val Asn Arg Ile AspMet Val Asn Leu Asp Gly Ser Tyr 5145 5150 5155 CGG GTT ACC CTT ATA ACTGAA AAC TTG GGG CAT CCT AGA GGA ATT GCC 1652 Arg Val Thr Leu Ile Thr GluAsn Leu Gly His Pro Arg Gly Ile Ala 5160 5165 5170 GTG GAC CCA ACT GTTGGT TAT TTA TTT TTC TCA GAT TGG GAG AGC CTT 1700 Val Asp Pro Thr Val GlyTyr Leu Phe Phe Ser Asp Trp Glu Ser Leu 5175 5180 5185 TCT GGG GAA CCTAAG CTG GAA AGG GCA TTC ATG GAT GGC AGC AAC CGT 1748 Ser Gly Glu Pro LysLeu Glu Arg Ala Phe Met Asp Gly Ser Asn Arg 5190 5195 5200 AAA GAC TTGGTG AAA ACA AAG CTG GGA TGG CCT GCT GGG GTA ACT CTG 1796 Lys Asp Leu ValLys Thr Lys Leu Gly Trp Pro Ala Gly Val Thr Leu 5205 5210 5215 5220 GATATG ATA TCG AAG CGT GTT TAC TGG GTT GAC TCT CGG TTT GAT TAC 1844 Asp MetIle Ser Lys Arg Val Tyr Trp Val Asp Ser Arg Phe Asp Tyr 5225 5230 5235ATT GAA ACT GTA ACT TAT GAT GGA ATT CAA AGG AAG ACT GTA GTT CAT 1892 IleGlu Thr Val Thr Tyr Asp Gly Ile Gln Arg Lys Thr Val Val His 5240 52455250 GGA GGC TCC CTC ATT CCT CAT CCC TTT GGA GTA AGC TTA TTT GAA GGT1940 Gly Gly Ser Leu Ile Pro His Pro Phe Gly Val Ser Leu Phe Glu Gly5255 5260 5265 CAG GTG TTC TTT ACA GAT TGG ACA AAG ATG GCC GTG CTG AAGGCA AAC 1988 Gln Val Phe Phe Thr Asp Trp Thr Lys Met Ala Val Leu Lys AlaAsn 5270 5275 5280 AAG TTC ACA GAG ACC AAC CCA CAA GTG TAC TAC CAG GCTTCC CTG AGG 2036 Lys Phe Thr Glu Thr Asn Pro Gln Val Tyr Tyr Gln Ala SerLeu Arg 5285 5290 5295 5300 CCC TAT GGA GTG ACT GTT TAC CAT TCC CTC AGACAG CCC TAT GCT ACC 2084 Pro Tyr Gly Val Thr Val Tyr His Ser Leu Arg GlnPro Tyr Ala Thr 5305 5310 5315 AAT CCG TGT AAA GAT AAC AAT GGG GGC TGTGAG CAG GTC TGT GTT CTC 2132 Asn Pro Cys Lys Asp Asn Asn Gly Gly Cys GluGln Val Cys Val Leu 5320 5325 5330 AGC CAC AGA ACA GAT AAT GAT GGT TTGGGT TTC CGT TGC AAG TGC ACA 2180 Ser His Arg Thr Asp Asn Asp Gly Leu GlyPhe Arg Cys Lys Cys Thr 5335 5340 5345 TTC GGC TTC CAA CTG GAT ACA GATGAG CGC CAC TGC ATT GCT GTT CAG 2228 Phe Gly Phe Gln Leu Asp Thr Asp GluArg His Cys Ile Ala Val Gln 5350 5355 5360 AAT TTC CTC ATT TTT TCA TCCCAA GTT GCT ATT CGT GGG ATC CCG TTC 2276 Asn Phe Leu Ile Phe Ser Ser GlnVal Ala Ile Arg Gly Ile Pro Phe 5365 5370 5375 5380 ACC TTG TCT ACC CAGGAA GAT GTC ATG GTT CCA GTT TCG GGG AAT CCT 2324 Thr Leu Ser Thr Gln GluAsp Val Met Val Pro Val Ser Gly Asn Pro 5385 5390 5395 TCT TTC TTT GTCGGG ATT GAT TTT GAC GCC CAG GAC AGC ACT ATC TTT 2372 Ser Phe Phe Val GlyIle Asp Phe Asp Ala Gln Asp Ser Thr Ile Phe 5400 5405 5410 TTT TCA GATATG TCA AAA CAC ATG ATT TTT AAG CAA AAG ATT GAT GGC 2420 Phe Ser Asp MetSer Lys His Met Ile Phe Lys Gln Lys Ile Asp Gly 5415 5420 5425 ACA GGAAGA GAA ATT CTC GCA GCT AAC AGG GTG GAA AAT GTT GAA AGT 2468 Thr Gly ArgGlu Ile Leu Ala Ala Asn Arg Val Glu Asn Val Glu Ser 5430 5435 5440 TTGGCT TTT GAT TGG ATT TCA AAG AAT CTC TAT TGG ACA GAC TCT CAT 2516 Leu AlaPhe Asp Trp Ile Ser Lys Asn Leu Tyr Trp Thr Asp Ser His 5445 5450 54555460 TAC AAG AGT ATC AGT GTC ATG AGG CTA GCT GAT AAA ACG AGA CGC ACA2564 Tyr Lys Ser Ile Ser Val Met Arg Leu Ala Asp Lys Thr Arg Arg Thr5465 5470 5475 GTA GTT CAG TAT TTA AAT AAC CCA CGG TCG GTG GTA GTT CATCCT TTT 2612 Val Val Gln Tyr Leu Asn Asn Pro Arg Ser Val Val Val His ProPhe 5480 5485 5490 GCC GGG TAT CTA TTC TTC ACT GAT TGG TTC CGT CCT GCTAAA ATT ATG 2660 Ala Gly Tyr Leu Phe Phe Thr Asp Trp Phe Arg Pro Ala LysIle Met 5495 5500 5505 AGA GCA TGG AGT GAC GGA TCT CAC CTC TTG CCT GTAATA AAC ACT ACT 2708 Arg Ala Trp Ser Asp Gly Ser His Leu Leu Pro Val IleAsn Thr Thr 5510 5515 5520 CTT GGA TGG CCC AAT GGC TTG GCC ATC GAT TGGGCT GCT TCA CGA TTG 2756 Leu Gly Trp Pro Asn Gly Leu Ala Ile Asp Trp AlaAla Ser Arg Leu 5525 5530 5535 5540 TAC TGG GTA GAT GCC TAT TTT GAT AAAATT GAG CAC AGC ACC TTT GAT 2804 Tyr Trp Val Asp Ala Tyr Phe Asp Lys IleGlu His Ser Thr Phe Asp 5545 5550 5555 GGT TTA GAC AGA AGA AGA CTG GGCCAT ATA GAG CAG ATG ACA CAT CCG 2852 Gly Leu Asp Arg Arg Arg Leu Gly HisIle Glu Gln Met Thr His Pro 5560 5565 5570 TTT GGA CTT GCC ATC TTT GGAGAG CAT TTA TTT TTT ACT GAC TGG AGA 2900 Phe Gly Leu Ala Ile Phe Gly GluHis Leu Phe Phe Thr Asp Trp Arg 5575 5580 5585 CTG GGT GCC ATT ATT CGAGTC AGG AAA GCA GAT GGT GGA GAA ATG ACA 2948 Leu Gly Ala Ile Ile Arg ValArg Lys Ala Asp Gly Gly Glu Met Thr 5590 5595 5600 GTT ATC CGA AGT GGCATT GCT TAC ATA CTG CAT TTG AAA TCG TAT GAT 2996 Val Ile Arg Ser Gly IleAla Tyr Ile Leu His Leu Lys Ser Tyr Asp 5605 5610 5615 5620 GTC AAC ATCCAG ACT GGT TCT AAC GCC TGT AAT CAA CCC ACG CAT CCT 3044 Val Asn Ile GlnThr Gly Ser Asn Ala Cys Asn Gln Pro Thr His Pro 5625 5630 5635 AAC GGTGAC TGC AGC CAC TTC TGC TTC CCG GTG CCA AAT TTC CAG CGA 3092 Asn Gly AspCys Ser His Phe Cys Phe Pro Val Pro Asn Phe Gln Arg 5640 5645 5650 GTGTGT GGG TGC CCT TAT GGA ATG AGG CTG GCT TCC AAT CAC TTG ACA 3140 Val CysGly Cys Pro Tyr Gly Met Arg Leu Ala Ser Asn His Leu Thr 5655 5660 5665TGC GAG GGG GAC CCA ACC AAT GAA CCA CCC ACG GAG CAG TGT GGC TTA 3188 CysGlu Gly Asp Pro Thr Asn Glu Pro Pro Thr Glu Gln Cys Gly Leu 5670 56755680 TTT TCC TTC CCC TGT AAA AAT GGC AGA TGT GTG CCC AAT TAC TAT CTC3236 Phe Ser Phe Pro Cys Lys Asn Gly Arg Cys Val Pro Asn Tyr Tyr Leu5685 5690 5695 5700 TGT GAT GGA GTC GAT GAT TGT CAT GAT AAC AGT GAT GAGCAA CTA TGT 3284 Cys Asp Gly Val Asp Asp Cys His Asp Asn Ser Asp Glu GlnLeu Cys 5705 5710 5715 GGC ACA CTT AAT AAT ACC TGT TCA TCT TCG GCG TTCACC TGT GGC CAT 3332 Gly Thr Leu Asn Asn Thr Cys Ser Ser Ser Ala Phe ThrCys Gly His 5720 5725 5730 GGG GAG TGC ATT CCT GCA CAC TGG CGC TGT GACAAA CGC AAC GAC TGT 3380 Gly Glu Cys Ile Pro Ala His Trp Arg Cys Asp LysArg Asn Asp Cys 5735 5740 5745 GTG GAT GGC AGT GAT GAG CAC AAC TGC CCCACC CAC GCA CCT GCT TCC 3428 Val Asp Gly Ser Asp Glu His Asn Cys Pro ThrHis Ala Pro Ala Ser 5750 5755 5760 TGC CTT GAC ACC CAA TAC ACC TGT GATAAT CAC CAG TGT ATC TCA AAG 3476 Cys Leu Asp Thr Gln Tyr Thr Cys Asp AsnHis Gln Cys Ile Ser Lys 5765 5770 5775 5780 AAC TGG GTC TGT GAC ACA GACAAT GAT TGT GGG GAT GGA TCT GAT GAA 3524 Asn Trp Val Cys Asp Thr Asp AsnAsp Cys Gly Asp Gly Ser Asp Glu 5785 5790 5795 AAG AAC TGC AAT TCG ACAGAG ACA TGC CAA CCT AGT CAG TTT AAT TGC 3572 Lys Asn Cys Asn Ser Thr GluThr Cys Gln Pro Ser Gln Phe Asn Cys 5800 5805 5810 CCC AAT CAT CGA TGTATT GAC CTA TCG TTT GTC TGT GAT GGT GAC AAG 3620 Pro Asn His Arg Cys IleAsp Leu Ser Phe Val Cys Asp Gly Asp Lys 5815 5820 5825 GAT TGT GTT GATGGA TCT GAT GAG GTT GGT TGT GTA TTA AAC TGT ACT 3668 Asp Cys Val Asp GlySer Asp Glu Val Gly Cys Val Leu Asn Cys Thr 5830 5835 5840 GCT TCT CAATTC AAG TGT GCC AGT GGG GAT AAA TGT ATT GGC GTC ACA 3716 Ala Ser Gln PheLys Cys Ala Ser Gly Asp Lys Cys Ile Gly Val Thr 5845 5850 5855 5860 AATCGT TGT GAT GGT GTT TTT GAT TGC AGT GAC AAC TCG GAT GAA GCG 3764 Asn ArgCys Asp Gly Val Phe Asp Cys Ser Asp Asn Ser Asp Glu Ala 5865 5870 5875GGC TGT CCA ACC AGG CCT CCT GGT ATG TGC CAC TCA GAT GAA TTT CAG 3812 GlyCys Pro Thr Arg Pro Pro Gly Met Cys His Ser Asp Glu Phe Gln 5880 58855890 TGC CAA GAA GAT GGT ATC TGC ATC CCG AAC TTC TGG GAA TGT GAT GGG3860 Cys Gln Glu Asp Gly Ile Cys Ile Pro Asn Phe Trp Glu Cys Asp Gly5895 5900 5905 CAT CCA GAC TGC CTC TAT GGA TCT GAT GAG CAC AAT GCC TGTGTC CCC 3908 His Pro Asp Cys Leu Tyr Gly Ser Asp Glu His Asn Ala Cys ValPro 5910 5915 5920 AAG ACT TGC CCT TCA TCA TAT TTC CAC TGT GAC AAC GGAAAC TGC ATC 3956 Lys Thr Cys Pro Ser Ser Tyr Phe His Cys Asp Asn Gly AsnCys Ile 5925 5930 5935 5940 CAC AGG GCA TGG CTC TGT GAT CGG GAC AAT GACTGC GGG GAT ATG AGT 4004 His Arg Ala Trp Leu Cys Asp Arg Asp Asn Asp CysGly Asp Met Ser 5945 5950 5955 GAT GAG AAG GAC TGC CCT ACT CAG CCC TTTCGC TGT CCT AGT TGG CAA 4052 Asp Glu Lys Asp Cys Pro Thr Gln Pro Phe ArgCys Pro Ser Trp Gln 5960 5965 5970 TGG CAG TGT CTT GGC CAT AAC ATC TGTGTG AAT CTG AGT GTA GTG TGT 4100 Trp Gln Cys Leu Gly His Asn Ile Cys ValAsn Leu Ser Val Val Cys 5975 5980 5985 GAT GGC ATC TTT GAC TGC CCC AATGGG ACA GAT GAG TCC CCA CTT TGC 4148 Asp Gly Ile Phe Asp Cys Pro Asn GlyThr Asp Glu Ser Pro Leu Cys 5990 5995 6000 AAT GGG AAC AGC TGC TCA GATTTC AAT GGT GGT TGT ACT CAC GAG TGT 4196 Asn Gly Asn Ser Cys Ser Asp PheAsn Gly Gly Cys Thr His Glu Cys 6005 6010 6015 6020 GTT CAA GAG CCC TTTGGG GCT AAA TGC CTA TGT CCA TTG GGA TTC TTA 4244 Val Gln Glu Pro Phe GlyAla Lys Cys Leu Cys Pro Leu Gly Phe Leu 6025 6030 6035 CTT GCC AAT GATTCT AAG ACC TGT GAA GAC ATA GAT GAA TGT GAT ATT 4292 Leu Ala Asn Asp SerLys Thr Cys Glu Asp Ile Asp Glu Cys Asp Ile 6040 6045 6050 CTA GGC TCTTGT AGC CAG CAC TGT TAC AAT ATG AGA GGT TCT TTC CGG 4340 Leu Gly Ser CysSer Gln His Cys Tyr Asn Met Arg Gly Ser Phe Arg 6055 6060 6065 TGC TCGTGT GAT ACA GGC TAC ATG TTA GAA AGT GAT GGG AGG ACT TGC 4388 Cys Ser CysAsp Thr Gly Tyr Met Leu Glu Ser Asp Gly Arg Thr Cys 6070 6075 6080 AAAGTT ACA GCA TCT GAG AGT CTG CTG TTA CTT GTG GCA AGT CAG AAC 4436 Lys ValThr Ala Ser Glu Ser Leu Leu Leu Leu Val Ala Ser Gln Asn 6085 6090 60956100 AAA ATT ATT GCC GAC AGT GTC ACC TCC CAG GTC CAC AAT ATC TAT TCA4484 Lys Ile Ile Ala Asp Ser Val Thr Ser Gln Val His Asn Ile Tyr Ser6105 6110 6115 TTG GTC GAG AAT GGT TCT TAC ATT GTA GCT GTT GAT TTT GATTCA ATT 4532 Leu Val Glu Asn Gly Ser Tyr Ile Val Ala Val Asp Phe Asp SerIle 6120 6125 6130 AGT GGT CGT ATC TTT TGG TCT GAT GCA ACT CAG GGT AAAACC TGG AGT 4580 Ser Gly Arg Ile Phe Trp Ser Asp Ala Thr Gln Gly Lys ThrTrp Ser 6135 6140 6145 GCG TTT CAA AAT GGA ACG GAC AGA AGA GTG GTA TTTGAC AGT AGC ATC 4628 Ala Phe Gln Asn Gly Thr Asp Arg Arg Val Val Phe AspSer Ser Ile 6150 6155 6160 ATC TTG ACT GAA ACT ATT GCA ATA GAT TGG GTAGGT CGT AAT CTT TAC 4676 Ile Leu Thr Glu Thr Ile Ala Ile Asp Trp Val GlyArg Asn Leu Tyr 6165 6170 6175 6180 TGG ACA GAC TAT GCT CTG GAA ACA ATTGAA GTC TCC AAA ATT GAT GGG 4724 Trp Thr Asp Tyr Ala Leu Glu Thr Ile GluVal Ser Lys Ile Asp Gly 6185 6190 6195 AGC CAC AGG ACT GTG CTG ATT AGTAAA AAC CTA ACA AAT CCA AGA GGA 4772 Ser His Arg Thr Val Leu Ile Ser LysAsn Leu Thr Asn Pro Arg Gly 6200 6205 6210 CTA GCA TTA GAT CCC AGA ATGAAT GAG CAT CTA CTG TTC TGG TCT GAC 4820 Leu Ala Leu Asp Pro Arg Met AsnGlu His Leu Leu Phe Trp Ser Asp 6215 6220 6225 TGG GGC CAC CAC CCT CGCATC GAG CGA GCC AGC ATG GAC GGC AGC ATG 4868 Trp Gly His His Pro Arg IleGlu Arg Ala Ser Met Asp Gly Ser Met 6230 6235 6240 CGC ACT GTC ATT GTCCAG GAC AAG ATC TTC TGG CCC TGC GGC TTA ACT 4916 Arg Thr Val Ile Val GlnAsp Lys Ile Phe Trp Pro Cys Gly Leu Thr 6245 6250 6255 6260 ATT GAC TACCCC AAC AGA CTG CTC TAC TTC ATG GAC TCC TAT CTT GAT 4964 Ile Asp Tyr ProAsn Arg Leu Leu Tyr Phe Met Asp Ser Tyr Leu Asp 6265 6270 6275 TAC ATGGAC TTT TGC GAT TAT AAT GGA CAC CAT CGG AGA CAG GTG ATA 5012 Tyr Met AspPhe Cys Asp Tyr Asn Gly His His Arg Arg Gln Val Ile 6280 6285 6290 GCCAGT GAT TTG ATT ATA CGG CAC CCC TAT GCC CTA ACT CTC TTT GAA 5060 Ala SerAsp Leu Ile Ile Arg His Pro Tyr Ala Leu Thr Leu Phe Glu 6295 6300 6305GAC TCT GTG TAC TGG ACT GAC CGT GCT ACT CGT CGG GTT ATG CGA GCC 5108 AspSer Val Tyr Trp Thr Asp Arg Ala Thr Arg Arg Val Met Arg Ala 6310 63156320 AAC AAG TGG CAT GGA GGG AAC CAG TCA GTT GTA ATG TAT AAT ATT CAA5156 Asn Lys Trp His Gly Gly Asn Gln Ser Val Val Met Tyr Asn Ile Gln6325 6330 6335 6340 TGG CCC CTT GGG ATT GTT GCG GTT CAT CCT TCG AAA CAACCA AAT TCC 5204 Trp Pro Leu Gly Ile Val Ala Val His Pro Ser Lys Gln ProAsn Ser 6345 6350 6355 GTG AAT CCA TGT GCC TTT TCC CGC TGC AGC CAT CTCTGC CTG CTT TCC 5252 Val Asn Pro Cys Ala Phe Ser Arg Cys Ser His Leu CysLeu Leu Ser 6360 6365 6370 TCA CAG GGG CCT CAT TTT TAC TCC TGT GTT TGTCCT TCA GGA TGG AGT 5300 Ser Gln Gly Pro His Phe Tyr Ser Cys Val Cys ProSer Gly Trp Ser 6375 6380 6385 CTG TCT CCT GAT CTC CTG AAT TGC TTG AGAGAT GAT CAA CCT TTC TTA 5348 Leu Ser Pro Asp Leu Leu Asn Cys Leu Arg AspAsp Gln Pro Phe Leu 6390 6395 6400 ATA ACT GTA AGG CAA CAT ATA ATT TTTGGA ATC TCC CTT AAT CCT GAG 5396 Ile Thr Val Arg Gln His Ile Ile Phe GlyIle Ser Leu Asn Pro Glu 6405 6410 6415 6420 GTG AAG AGC AAT GAT GCT ATGGTC CCC ATA GCA GGG ATA CAG AAT GGT 5444 Val Lys Ser Asn Asp Ala Met ValPro Ile Ala Gly Ile Gln Asn Gly 6425 6430 6435 TTA GAT GTT GAA TTT GATGAT GCT GAG CAA TAC ATC TAT TGG GTT GAA 5492 Leu Asp Val Glu Phe Asp AspAla Glu Gln Tyr Ile Tyr Trp Val Glu 6440 6445 6450 AAT CCA GGT GAA ATTCAC AGA GTG AAG ACA GAT GGC ACC AAC AGG ACA 5540 Asn Pro Gly Glu Ile HisArg Val Lys Thr Asp Gly Thr Asn Arg Thr 6455 6460 6465 GTA TTT GCT TCTATA TCT ATG GTG GGG CCT TCT ATG AAC CTG GCC TTA 5588 Val Phe Ala Ser IleSer Met Val Gly Pro Ser Met Asn Leu Ala Leu 6470 6475 6480 GAT TGG ATTTCA AGA AAC CTT TAT TCT ACC AAT CCT AGA ACT CAG TCA 5636 Asp Trp Ile SerArg Asn Leu Tyr Ser Thr Asn Pro Arg Thr Gln Ser 6485 6490 6495 6500 ATCGAG GTT TTG ACA CTC CAC GGA GAT ATC AGA TAC AGA AAA ACA TTG 5684 Ile GluVal Leu Thr Leu His Gly Asp Ile Arg Tyr Arg Lys Thr Leu 6505 6510 6515ATT GCC AAT GAT GGG ACA GCT CTT GGA GTT GGC TTT CCA ATT GGC ATA 5732 IleAla Asn Asp Gly Thr Ala Leu Gly Val Gly Phe Pro Ile Gly Ile 6520 65256530 ACT GTT GAT CCT GCT CGT GGG AAG CTG TAC TGG TCA GAC CAA GGA ACT5780 Thr Val Asp Pro Ala Arg Gly Lys Leu Tyr Trp Ser Asp Gln Gly Thr6535 6540 6545 GAC AGT GGG GTT CCT GCC AAG ATC GCC AGT GCT AAC ATG GATGGC ACA 5828 Asp Ser Gly Val Pro Ala Lys Ile Ala Ser Ala Asn Met Asp GlyThr 6550 6555 6560 TCT GTG AAA ACT CTC TTT ACT GGG AAC CTC GAA CAC CTGGAG TGT GTC 5876 Ser Val Lys Thr Leu Phe Thr Gly Asn Leu Glu His Leu GluCys Val 6565 6570 6575 6580 ACT CTT GAC ATC GAA GAG CAG AAA CTC TAC TGGGCA GTC ACT GGA AGA 5924 Thr Leu Asp Ile Glu Glu Gln Lys Leu Tyr Trp AlaVal Thr Gly Arg 6585 6590 6595 GGA GTG ATT GAA AGA GGA AAC GTG GAT GGAACA GAT CGG ATG ATC CTG 5972 Gly Val Ile Glu Arg Gly Asn Val Asp Gly ThrAsp Arg Met Ile Leu 6600 6605 6610 GTA CAC CAG CTT TCC CAC CCC TGG GGAATT GCA GTC CAT GAT TCT TTC 6020 Val His Gln Leu Ser His Pro Trp Gly IleAla Val His Asp Ser Phe 6615 6620 6625 CTT TAT TAT ACT GAT GAA CAG TATGAG GTC ATT GAA AGA GTT GAT AAG 6068 Leu Tyr Tyr Thr Asp Glu Gln Tyr GluVal Ile Glu Arg Val Asp Lys 6630 6635 6640 GCC ACT GGG GCC AAC AAA ATAGTC TTG AGA GAT AAT GTT CCA AAT CTG 6116 Ala Thr Gly Ala Asn Lys Ile ValLeu Arg Asp Asn Val Pro Asn Leu 6645 6650 6655 6660 AGG GGT CTT CAA GTTTAT CAC AGA CGC AAT GCC GCC GAA TCC TCA AAT 6164 Arg Gly Leu Gln Val TyrHis Arg Arg Asn Ala Ala Glu Ser Ser Asn 6665 6670 6675 GGC TGT AGC AACAAC ATG AAT GCC TGT CAG CAG ATT TGC CTG CCT GTA 6212 Gly Cys Ser Asn AsnMet Asn Ala Cys Gln Gln Ile Cys Leu Pro Val 6680 6685 6690 CCA GGA GGATTG TTT TCC TGC GCC TGT GCC ACT GGA TTT AAA CTC AAT 6260 Pro Gly Gly LeuPhe Ser Cys Ala Cys Ala Thr Gly Phe Lys Leu Asn 6695 6700 6705 CCT GATAAT CGG TCC TGC TCT CCA TAT AAC TCT TTC ATT GTT GTT TCA 6308 Pro Asp AsnArg Ser Cys Ser Pro Tyr Asn Ser Phe Ile Val Val Ser 6710 6715 6720 ATGCTG TCT GCA ATC AGA GGC TTT AGC TTG GAA TTG TCA GAT CAT TCA 6356 Met LeuSer Ala Ile Arg Gly Phe Ser Leu Glu Leu Ser Asp His Ser 6725 6730 67356740 GAA ACC ATG GTG CCG GTG GCA GGC CAA GGA CGA AAC GCA CTG CAT GTG6404 Glu Thr Met Val Pro Val Ala Gly Gln Gly Arg Asn Ala Leu His Val6745 6750 6755 GAT GTG GAT GTG TCC TCT GGC TTT ATT TAT TGG TGT GAT TTTAGC AGC 6452 Asp Val Asp Val Ser Ser Gly Phe Ile Tyr Trp Cys Asp Phe SerSer 6760 6765 6770 TCA GTG GCA TCT GAT AAT GCG ATC CGT AGA ATT AAA CCAGAT GGA TCT 6500 Ser Val Ala Ser Asp Asn Ala Ile Arg Arg Ile Lys Pro AspGly Ser 6775 6780 6785 TCT CTG ATG AAC ATT GTG ACA CAT GGA ATA GGA GAAAAT GGA GTC CGG 6548 Ser Leu Met Asn Ile Val Thr His Gly Ile Gly Glu AsnGly Val Arg 6790 6795 6800 GGT ATT GCA GTG GAT TGG GTA GCA GGA AAT CTTTAT TTC ACC AAT GCC 6596 Gly Ile Ala Val Asp Trp Val Ala Gly Asn Leu TyrPhe Thr Asn Ala 6805 6810 6815 6820 TTT GTT TCT GAA ACA CTG ATA GAA GTTCTG CGG ATC AAT ACT ACT TAC 6644 Phe Val Ser Glu Thr Leu Ile Glu Val LeuArg Ile Asn Thr Thr Tyr 6825 6830 6835 CGC CGT GTT CTT CTT AAA GTC ACAGTG GAC ATG CCT AGG CAT ATT GTT 6692 Arg Arg Val Leu Leu Lys Val Thr ValAsp Met Pro Arg His Ile Val 6840 6845 6850 GTA GAT CCC AAG AAC AGA TACCTC TTC TGG GCT GAC TAT GGG CAG AGA 6740 Val Asp Pro Lys Asn Arg Tyr LeuPhe Trp Ala Asp Tyr Gly Gln Arg 6855 6860 6865 CCA AAG ATT GAG CGT TCTTTC CTT GAC TGT ACC AAT CGA ACA GTG CTT 6788 Pro Lys Ile Glu Arg Ser PheLeu Asp Cys Thr Asn Arg Thr Val Leu 6870 6875 6880 GTG TCA GAG GGC ATTGTC ACA CCA CGG GGC TTG GCA GTG GAC CGA AGT 6836 Val Ser Glu Gly Ile ValThr Pro Arg Gly Leu Ala Val Asp Arg Ser 6885 6890 6895 6900 GAT GGC TACGTT TAT TGG GTT GAT GAT TCT TTA GAT ATA ATT GCA AGG 6884 Asp Gly Tyr ValTyr Trp Val Asp Asp Ser Leu Asp Ile Ile Ala Arg 6905 6910 6915 ATT CGTATC AAT GGA GAG AAC TCT GAA GTG ATT CGT TAT GGC AGT CGT 6932 Ile Arg IleAsn Gly Glu Asn Ser Glu Val Ile Arg Tyr Gly Ser Arg 6920 6925 6930 TACCCA ACT CCT TAT GGC ATC ACT GTT TTT GAA AAT TCT ATC ATA TGG 6980 Tyr ProThr Pro Tyr Gly Ile Thr Val Phe Glu Asn Ser Ile Ile Trp 6935 6940 6945GTA GAT AGG AAT TTG AAA AAG ATC TTC CAA GCC AGC AAG GAA CCA GAG 7028 ValAsp Arg Asn Leu Lys Lys Ile Phe Gln Ala Ser Lys Glu Pro Glu 6950 69556960 AAC ACA GAG CCA CCC ACA GTG ATA AGA GAC AAT ATC AAC TGG CTA AGA7076 Asn Thr Glu Pro Pro Thr Val Ile Arg Asp Asn Ile Asn Trp Leu Arg6965 6970 6975 6980 GAT GTG ACC ATC TTT GAC AAG CAA GTC CAG CCC CGG TCACCA GCA GAG 7124 Asp Val Thr Ile Phe Asp Lys Gln Val Gln Pro Arg Ser ProAla Glu 6985 6990 6995 GTC AAC AAC AAC CCT TGC TTG GAA AAC AAT GGT GGGTGC TCT CAT CTC 7172 Val Asn Asn Asn Pro Cys Leu Glu Asn Asn Gly Gly CysSer His Leu 7000 7005 7010 TGC TTT GCT CTG CCT GGA TTG CAC ACC CCA AAATGT GAC TGT GCC TTT 7220 Cys Phe Ala Leu Pro Gly Leu His Thr Pro Lys CysAsp Cys Ala Phe 7015 7020 7025 GGG ACC CTG CAA AGT GAT GGC AAG AAT TGTGCC ATT TCA ACA GAA AAT 7268 Gly Thr Leu Gln Ser Asp Gly Lys Asn Cys AlaIle Ser Thr Glu Asn 7030 7035 7040 TTC CTC ATC TTT GCC TTG TCT AAT TCCTTG AGA AGC TTA CAC TTG GAC 7316 Phe Leu Ile Phe Ala Leu Ser Asn Ser LeuArg Ser Leu His Leu Asp 7045 7050 7055 7060 CCT GAA AAC CAT AGC CCA CCTTTC CAA ACA ATA AAT GTG GAA AGA ACT 7364 Pro Glu Asn His Ser Pro Pro PheGln Thr Ile Asn Val Glu Arg Thr 7065 7070 7075 GTC ATG TCT CTA GAC TATGAC AGT GTA AGT GAT AGA ATC TAC TTC ACA 7412 Val Met Ser Leu Asp Tyr AspSer Val Ser Asp Arg Ile Tyr Phe Thr 7080 7085 7090 CAA AAT TTA GCC TCTGGA GTT GGA CAG ATT TCC TAT GCC ACC CTG TCT 7460 Gln Asn Leu Ala Ser GlyVal Gly Gln Ile Ser Tyr Ala Thr Leu Ser 7095 7100 7105 TCA GGG ATC CATACT CCA ACT GTC ATT GCT TCA GGT ATA GGG ACT GCT 7508 Ser Gly Ile His ThrPro Thr Val Ile Ala Ser Gly Ile Gly Thr Ala 7110 7115 7120 GAT GGC ATTGCC TTT GAC TGG ATT ACT AGA AGA ATT TAT TAC AGT GAC 7556 Asp Gly Ile AlaPhe Asp Trp Ile Thr Arg Arg Ile Tyr Tyr Ser Asp 7125 7130 7135 7140 TACCTC AAC CAG ATG ATT AAT TCC ATG GCT GAA GAT GGG TCT AAC CGC 7604 Tyr LeuAsn Gln Met Ile Asn Ser Met Ala Glu Asp Gly Ser Asn Arg 7145 7150 7155ACT GTG ATA GCC CGC GTT CCA AAA CCA AGA GCA ATT GTG TTA GAT CCC 7652 ThrVal Ile Ala Arg Val Pro Lys Pro Arg Ala Ile Val Leu Asp Pro 7160 71657170 TGC CAA GGG TAC CTG TAC TGG GCT GAC TGG GAT ACA CAT GCC AAA ATC7700 Cys Gln Gly Tyr Leu Tyr Trp Ala Asp Trp Asp Thr His Ala Lys Ile7175 7180 7185 GAG AGA GCC ACA TTG GGA GGA AAC TTC CGG GTA CCC ATT GTGAAC AGC 7748 Glu Arg Ala Thr Leu Gly Gly Asn Phe Arg Val Pro Ile Val AsnSer 7190 7195 7200 AGT CTG GTC ATG CCC AGT GGG CTG ACT CTG GAC TAT GAAGAG GAC CTT 7796 Ser Leu Val Met Pro Ser Gly Leu Thr Leu Asp Tyr Glu GluAsp Leu 7205 7210 7215 7220 CTC TAC TGG GTG GAT GCT AGT CTG CAG AGG ATTGAA CGC AGC ACT CTG 7844 Leu Tyr Trp Val Asp Ala Ser Leu Gln Arg Ile GluArg Ser Thr Leu 7225 7230 7235 ACG GGC GTG GAT CGT GAA GTC ATT GTC AATGCA GCC GTT CAT GCT TTT 7892 Thr Gly Val Asp Arg Glu Val Ile Val Asn AlaAla Val His Ala Phe 7240 7245 7250 GGC TTG ACT CTC TAT GGC CAG TAT ATTTAC TGG ACT GAC TTG TAC ACA 7940 Gly Leu Thr Leu Tyr Gly Gln Tyr Ile TyrTrp Thr Asp Leu Tyr Thr 7255 7260 7265 CAA AGA ATT TAC CGA GCT AAC AAATAT GAC GGG TCA GGT CAG ATT GCA 7988 Gln Arg Ile Tyr Arg Ala Asn Lys TyrAsp Gly Ser Gly Gln Ile Ala 7270 7275 7280 ATG ACC ACA AAT TTG CTC TCCCAG CCC AGG GGA ATC AAC ACT GTT GTG 8036 Met Thr Thr Asn Leu Leu Ser GlnPro Arg Gly Ile Asn Thr Val Val 7285 7290 7295 7300 AAG AAC CAG AAA CAACAG TGT AAC AAT CCT TGT GAA CAG TTT AAT GGG 8084 Lys Asn Gln Lys Gln GlnCys Asn Asn Pro Cys Glu Gln Phe Asn Gly 7305 7310 7315 GGC TGC AGC CATATC TGT GCA CCA GGT CCA AAT GGT GCC GAG TGC CAG 8132 Gly Cys Ser His IleCys Ala Pro Gly Pro Asn Gly Ala Glu Cys Gln 7320 7325 7330 TGT CCA CATGAG GGC AAC TGG TAT TTG GCC AAC AAC AGG AAG CAC TGC 8180 Cys Pro His GluGly Asn Trp Tyr Leu Ala Asn Asn Arg Lys His Cys 7335 7340 7345 ATT GTGGAC AAT GGT GAA CGA TGT GGT GCA TCT TCC TTC ACC TGC TCC 8228 Ile Val AspAsn Gly Glu Arg Cys Gly Ala Ser Ser Phe Thr Cys Ser 7350 7355 7360 AATGGG CGC TGC ATC TCG GAA GAG TGG AAG TGT GAT AAT GAC AAC GAC 8276 Asn GlyArg Cys Ile Ser Glu Glu Trp Lys Cys Asp Asn Asp Asn Asp 7365 7370 73757380 TGT GGG GAT GGC AGT GAT GAG ATG GAA AGT GTC TGT GCA CTT CAC ACC8324 Cys Gly Asp Gly Ser Asp Glu Met Glu Ser Val Cys Ala Leu His Thr7385 7390 7395 TGC TCA CCG ACA GCC TTC ACC TGT GCC AAT GGG CGA TGT GTCCAA TAC 8372 Cys Ser Pro Thr Ala Phe Thr Cys Ala Asn Gly Arg Cys Val GlnTyr 7400 7405 7410 TCT TAC CGC TGT GAT TAC TAC AAT GAC TGT GGT GAT GGCAGT GAT GAG 8420 Ser Tyr Arg Cys Asp Tyr Tyr Asn Asp Cys Gly Asp Gly SerAsp Glu 7415 7420 7425 GCA GGG TGC CTG TTC AGG GAC TGC AAT GCC ACC ACGGAG TTT ATG TGC 8468 Ala Gly Cys Leu Phe Arg Asp Cys Asn Ala Thr Thr GluPhe Met Cys 7430 7435 7440 AAT AAC AGA AGG TGC ATA CCT CGT GAG TTT ATCTGC AAT GGT GTA GAC 8516 Asn Asn Arg Arg Cys Ile Pro Arg Glu Phe Ile CysAsn Gly Val Asp 7445 7450 7455 7460 AAC TGC CAT GAT AAT AAC ACT TCA GATGAG AAA AAT TGC CCT GAT CGC 8564 Asn Cys His Asp Asn Asn Thr Ser Asp GluLys Asn Cys Pro Asp Arg 7465 7470 7475 ACT TGC CAG TCT GGA TAC ACA AAATGT CAT AAT TCA AAT ATT TGT ATT 8612 Thr Cys Gln Ser Gly Tyr Thr Lys CysHis Asn Ser Asn Ile Cys Ile 7480 7485 7490 CCT CGC GTT TAT TTG TGT GACGGA GAC AAT GAC TGT GGA GAT AAC AGT 8660 Pro Arg Val Tyr Leu Cys Asp GlyAsp Asn Asp Cys Gly Asp Asn Ser 7495 7500 7505 GAT GAA AAC CCT ACT TATTGC ACC ACT CAC ACA TGC AGC AGC AGT GAG 8708 Asp Glu Asn Pro Thr Tyr CysThr Thr His Thr Cys Ser Ser Ser Glu 7510 7515 7520 TTC CAA TGC GCA TCTGGG CGC TGT ATT CCT CAA CAT TGG TAT TGT GAT 8756 Phe Gln Cys Ala Ser GlyArg Cys Ile Pro Gln His Trp Tyr Cys Asp 7525 7530 7535 7540 CAA GAA ACAGAT TGT TTT GAT GCC TCT GAT GAA CCT GCC TCT TGT GGT 8804 Gln Glu Thr AspCys Phe Asp Ala Ser Asp Glu Pro Ala Ser Cys Gly 7545 7550 7555 CAC TCTGAG CGA ACA TGC CTA GCT GAT GAG TTC AAG TGT GAT GGT GGG 8852 His Ser GluArg Thr Cys Leu Ala Asp Glu Phe Lys Cys Asp Gly Gly 7560 7565 7570 AGGTGC ATC CCA AGC GAA TGG ATC TGT GAC GGT GAT AAT GAC TGT GGG 8900 Arg CysIle Pro Ser Glu Trp Ile Cys Asp Gly Asp Asn Asp Cys Gly 7575 7580 7585GAT ATG AGT GAC GAG GAT AAA AGG CAC CAG TGT CAG AAT CAA AAC TGC 8948 AspMet Ser Asp Glu Asp Lys Arg His Gln Cys Gln Asn Gln Asn Cys 7590 75957600 TCG GAT TCC GAG TTT CTC TGT GTA AAT GAC AGA CCT CCG GAC AGG AGG8996 Ser Asp Ser Glu Phe Leu Cys Val Asn Asp Arg Pro Pro Asp Arg Arg7605 7610 7615 7620 TGC ATT CCC CAG TCT TGG GTC TGT GAT GGC GAT GTG GATTGT ACT GAC 9044 Cys Ile Pro Gln Ser Trp Val Cys Asp Gly Asp Val Asp CysThr Asp 7625 7630 7635 GGC TAC GAT GAG AAT CAG AAT TGC ACC AGG AGA ACTTGC TCT GAA AAT 9092 Gly Tyr Asp Glu Asn Gln Asn Cys Thr Arg Arg Thr CysSer Glu Asn 7640 7645 7650 GAA TTC ACC TGT GGT TAC GGA CTG TGT ATC CCAAAG ATA TTC AGG TGT 9140 Glu Phe Thr Cys Gly Tyr Gly Leu Cys Ile Pro LysIle Phe Arg Cys 7655 7660 7665 GAC CGG CAC AAT GAC TGT GGT GAC TAT AGCGAC GAG AGG GGC TGC TTA 9188 Asp Arg His Asn Asp Cys Gly Asp Tyr Ser AspGlu Arg Gly Cys Leu 7670 7675 7680 TAC CAG ACT TGC CAA CAG AAT CAG TTTACC TGT CAG AAC GGG CGC TGC 9236 Tyr Gln Thr Cys Gln Gln Asn Gln Phe ThrCys Gln Asn Gly Arg Cys 7685 7690 7695 7700 ATT AGT AAA ACC TTC GTC TGTGAT GAG GAT AAT GAC TGT GGA GAC GGA 9284 Ile Ser Lys Thr Phe Val Cys AspGlu Asp Asn Asp Cys Gly Asp Gly 7705 7710 7715 TCT GAT GAG CTG ATG CACCTG TGC CAC ACC CCA GAA CCC ACG TGT CCA 9332 Ser Asp Glu Leu Met His LeuCys His Thr Pro Glu Pro Thr Cys Pro 7720 7725 7730 CCT CAC GAG TTC AAGTGT GAC AAT GGG CGC TGC ATC GAG ATG ATG AAA 9380 Pro His Glu Phe Lys CysAsp Asn Gly Arg Cys Ile Glu Met Met Lys 7735 7740 7745 CTC TGC AAC CACCTA GAT GAC TGT TTG GAC AAC AGC GAT GAG AAA GGC 9428 Leu Cys Asn His LeuAsp Asp Cys Leu Asp Asn Ser Asp Glu Lys Gly 7750 7755 7760 TGT GGC ATTAAT GAA TGC CAT GAC CCT TCA ATC AGT GGC TGC GAT CAC 9476 Cys Gly Ile AsnGlu Cys His Asp Pro Ser Ile Ser Gly Cys Asp His 7765 7770 7775 7780 AACTGC ACA GAC ACC TTA ACC AGT TTC TAT TGT TCC TGT CGT CCT GGT 9524 Asn CysThr Asp Thr Leu Thr Ser Phe Tyr Cys Ser Cys Arg Pro Gly 7785 7790 7795TAC AAG CTC ATG TCT GAC AAG CGG ACT TGT GTT GAT ATT GAT GAA TGC 9572 TyrLys Leu Met Ser Asp Lys Arg Thr Cys Val Asp Ile Asp Glu Cys 7800 78057810 ACA GAG ATG CCT TTT GTC TGT AGC CAG AAG TGT GAG AAT GTA ATA GGC9620 Thr Glu Met Pro Phe Val Cys Ser Gln Lys Cys Glu Asn Val Ile Gly7815 7820 7825 TCC TAC ATC TGT AAG TGT GCC CCA GGC TAC CTC CGA GAA CCAGAT GGA 9668 Ser Tyr Ile Cys Lys Cys Ala Pro Gly Tyr Leu Arg Glu Pro AspGly 7830 7835 7840 AAG ACC TGC CGG CAA AAC AGT AAC ATC GAA CCC TAT CTCATT TTT AGC 9716 Lys Thr Cys Arg Gln Asn Ser Asn Ile Glu Pro Tyr Leu IlePhe Ser 7845 7850 7855 7860 AAC CGT TAC TAT TTG AGA AAT TTA ACT ATA GATGGC TAT TTT TAC TCC 9764 Asn Arg Tyr Tyr Leu Arg Asn Leu Thr Ile Asp GlyTyr Phe Tyr Ser 7865 7870 7875 CTC ATC TTG GAA GGA CTG GAC AAT GTT GTGGCA TTA GAT TTT GAC CGA 9812 Leu Ile Leu Glu Gly Leu Asp Asn Val Val AlaLeu Asp Phe Asp Arg 7880 7885 7890 GTA GAG AAG AGA TTG TAT TGG ATT GATACA CAG AGG CAA GTC ATT GAG 9860 Val Glu Lys Arg Leu Tyr Trp Ile Asp ThrGln Arg Gln Val Ile Glu 7895 7900 7905 AGA ATG TTT CTG AAT AAG ACA AACAAG GAG ACA ATC ATA AAC CAC AGA 9908 Arg Met Phe Leu Asn Lys Thr Asn LysGlu Thr Ile Ile Asn His Arg 7910 7915 7920 CTA CCA GCT GCA GAA AGT CTGGCT GTA GAC TGG GTT TCC AGA AAG CTC 9956 Leu Pro Ala Ala Glu Ser Leu AlaVal Asp Trp Val Ser Arg Lys Leu 7925 7930 7935 7940 TAC TGG TTG GAT GCCCGC CTG GAT GGC CTC TTT GTC TCT GAC CTC AAT 10004 Tyr Trp Leu Asp AlaArg Leu Asp Gly Leu Phe Val Ser Asp Leu Asn 7945 7950 7955 GGT GGA CACCGC CGC ATG CTG GCC CAG CAC TGT GTG GAT GCC AAC AAC 10052 Gly Gly HisArg Arg Met Leu Ala Gln His Cys Val Asp Ala Asn Asn 7960 7965 7970 ACCTTC TGC TTT GAT AAT CCC AGA GGA CTT GCC CTT CAC CCT CAA TAT 10100 ThrPhe Cys Phe Asp Asn Pro Arg Gly Leu Ala Leu His Pro Gln Tyr 7975 79807985 GGG TAC CTC TAC TGG GCA GAC TGG GGT CAC CGC GCA TAC ATT GGG AGA10148 Gly Tyr Leu Tyr Trp Ala Asp Trp Gly His Arg Ala Tyr Ile Gly Arg7990 7995 8000 GTA GGC ATG GAT GGA ACC AAC AAG TCT GTG ATA ATC TCC ACCAAG TTA 10196 Val Gly Met Asp Gly Thr Asn Lys Ser Val Ile Ile Ser ThrLys Leu 8005 8010 8015 8020 GAG TGG CCT AAT GGC ATC ACC ATT GAT TAC ACCAAT GAT CTA CTC TAC 10244 Glu Trp Pro Asn Gly Ile Thr Ile Asp Tyr ThrAsn Asp Leu Leu Tyr 8025 8030 8035 TGG GCA GAT GCC CAC CTG GGT TAC ATAGAG TAC TCT GAT TTG GAG GGC 10292 Trp Ala Asp Ala His Leu Gly Tyr IleGlu Tyr Ser Asp Leu Glu Gly 8040 8045 8050 CAC CAT CGA CAC ACG GTG TATGAT GGG GCA CTG CCT CAC CCT TTC GCT 10340 His His Arg His Thr Val TyrAsp Gly Ala Leu Pro His Pro Phe Ala 8055 8060 8065 ATT ACC ATT TTT GAAGAC ACT ATT TAT TGG ACA GAT TGG AAT ACA AGG 10388 Ile Thr Ile Phe GluAsp Thr Ile Tyr Trp Thr Asp Trp Asn Thr Arg 8070 8075 8080 ACA GTG GAAAAG GGA AAC AAA TAT GAT GGA TCA AAT AGA CAG ACA CTG 10436 Thr Val GluLys Gly Asn Lys Tyr Asp Gly Ser Asn Arg Gln Thr Leu 8085 8090 8095 8100GTG AAC ACA ACA CAC AGA CCA TTT GAC ATC CAT GTG TAC CAT CCA TAT 10484Val Asn Thr Thr His Arg Pro Phe Asp Ile His Val Tyr His Pro Tyr 81058110 8115 AGG CAG CCC ATT GTG AGC AAT CCC TGT GGT ACC AAC AAT GGT GGCTGT 10532 Arg Gln Pro Ile Val Ser Asn Pro Cys Gly Thr Asn Asn Gly GlyCys 8120 8125 8130 TCT CAT CTC TGC CTC ATC AAG CCA GGA GGA AAA GGG TTCACT TGC GAG 10580 Ser His Leu Cys Leu Ile Lys Pro Gly Gly Lys Gly PheThr Cys Glu 8135 8140 8145 TGT CCA GAT GAC TTC CGC ACC CTT CAA CTG AGTGGC AGC ACC TAC TGC 10628 Cys Pro Asp Asp Phe Arg Thr Leu Gln Leu SerGly Ser Thr Tyr Cys 8150 8155 8160 ATG CCC ATG TGC TCC AGC ACC CAG TTCCTG TGC GCT AAC AAT GAA AAG 10676 Met Pro Met Cys Ser Ser Thr Gln PheLeu Cys Ala Asn Asn Glu Lys 8165 8170 8175 8180 TGC ATT CCT ATC TGG TGGAAA TGT GAT GGA CAG AAA GAC TGC TCA GAT 10724 Cys Ile Pro Ile Trp TrpLys Cys Asp Gly Gln Lys Asp Cys Ser Asp 8185 8190 8195 GGC TCT GAT GAACTG GCC CTT TGC CCG CAG CGC TTC TGC CGA CTG GGA 10772 Gly Ser Asp GluLeu Ala Leu Cys Pro Gln Arg Phe Cys Arg Leu Gly 8200 8205 8210 CAG TTCCAG TGC AGT GAC GGC AAC TGC ACC AGC CCG CAG ACT TTA TGC 10820 Gln PheGln Cys Ser Asp Gly Asn Cys Thr Ser Pro Gln Thr Leu Cys 8215 8220 8225AAT GCT CAC CAA AAT TGC CCT GAT GGG TCT GAT GAA GAC CGT CTT CTT 10868Asn Ala His Gln Asn Cys Pro Asp Gly Ser Asp Glu Asp Arg Leu Leu 82308235 8240 TGT GAG AAT CAC CAC TGT GAC TCC AAT GAA TGG CAG TGC GCC AACAAA 10916 Cys Glu Asn His His Cys Asp Ser Asn Glu Trp Gln Cys Ala AsnLys 8245 8250 8255 8260 CGT TGC ATC CCA GAA TCC TGG CAG TGT GAC ACA TTTAAC GAC TGT GAG 10964 Arg Cys Ile Pro Glu Ser Trp Gln Cys Asp Thr PheAsn Asp Cys Glu 8265 8270 8275 GAT AAC TCA GAT GAA GAC AGT TCC CAC TGTGCC AGC AGG ACC TGC CGG 11012 Asp Asn Ser Asp Glu Asp Ser Ser His CysAla Ser Arg Thr Cys Arg 8280 8285 8290 CCG GGC CAG TTT CGG TGT GCT AATGGC CGC TGC ATC CCG CAG GCC TGG 11060 Pro Gly Gln Phe Arg Cys Ala AsnGly Arg Cys Ile Pro Gln Ala Trp 8295 8300 8305 AAG TGT GAT GTG GAT AATGAT TGT GGA GAC CAC TCG GAT GAG CCC ATT 11108 Lys Cys Asp Val Asp AsnAsp Cys Gly Asp His Ser Asp Glu Pro Ile 8310 8315 8320 GAA GAA TGC ATGAGC TCT GCC CAT CTC TGT GAC AAC TTC ACA GAA TTC 11156 Glu Glu Cys MetSer Ser Ala His Leu Cys Asp Asn Phe Thr Glu Phe 8325 8330 8335 8340 AGCTGC AAA ACA AAT TAC CGC TGC ATC CCA AAG TGG GCC GTG TGC AAT 11204 SerCys Lys Thr Asn Tyr Arg Cys Ile Pro Lys Trp Ala Val Cys Asn 8345 83508355 GGT GTA GAT GAC TGC AGG GAC AAC AGT GAT GAG CAA GGC TGT GAG GAG11252 Gly Val Asp Asp Cys Arg Asp Asn Ser Asp Glu Gln Gly Cys Glu Glu8360 8365 8370 AGG ACA TGC CAT CCT GTG GGG GAT TTC CGC TGT AAA AAT CACCAC TGC 11300 Arg Thr Cys His Pro Val Gly Asp Phe Arg Cys Lys Asn HisHis Cys 8375 8380 8385 ATC CCT CTT CGT TGG CAG TGT GAT GGG CAA AAT GACTGT GGA GAT AAC 11348 Ile Pro Leu Arg Trp Gln Cys Asp Gly Gln Asn AspCys Gly Asp Asn 8390 8395 8400 TCA GAT GAG GAA AAC TGT GCT CCC CGG GAGTGC ACA GAG AGC GAG TTT 11396 Ser Asp Glu Glu Asn Cys Ala Pro Arg GluCys Thr Glu Ser Glu Phe 8405 8410 8415 8420 CGA TGT GTC AAT CAG CAG TGCATT CCC TCG CGA TGG ATC TGT GAC CAT 11444 Arg Cys Val Asn Gln Gln CysIle Pro Ser Arg Trp Ile Cys Asp His 8425 8430 8435 TAC AAC GAC TGT GGGGAC AAC TCA GAT GAA CGG GAC TGT GAG ATG AGG 11492 Tyr Asn Asp Cys GlyAsp Asn Ser Asp Glu Arg Asp Cys Glu Met Arg 8440 8445 8450 ACC TGC CATCCT GAA TAT TTT CAG TGT ACA AGT GGA CAT TGT GTA CAC 11540 Thr Cys HisPro Glu Tyr Phe Gln Cys Thr Ser Gly His Cys Val His 8455 8460 8465 AGTGAA CTG AAA TGC GAT GGA TCC GCT GAC TGT TTG GAT GCG TCT GAT 11588 SerGlu Leu Lys Cys Asp Gly Ser Ala Asp Cys Leu Asp Ala Ser Asp 8470 84758480 GAA GCT GAT TGT CCC ACA CGC TTT CCT GAT GGT GCA TAC TGC CAG GCT11636 Glu Ala Asp Cys Pro Thr Arg Phe Pro Asp Gly Ala Tyr Cys Gln Ala8485 8490 8495 8500 ACT ATG TTC GAA TGC AAA AAC CAT GTT TGT ATC CCG CCATAT TGG AAA 11684 Thr Met Phe Glu Cys Lys Asn His Val Cys Ile Pro ProTyr Trp Lys 8505 8510 8515 TGT GAT GGC GAT GAT GAC TGT GGC GAT GGT TCAGAT GAA GAA CTT CAC 11732 Cys Asp Gly Asp Asp Asp Cys Gly Asp Gly SerAsp Glu Glu Leu His 8520 8525 8530 CTG TGC TTG GAT GTT CCC TGT AAT TCACCA AAC CGT TTC CGG TGT GAC 11780 Leu Cys Leu Asp Val Pro Cys Asn SerPro Asn Arg Phe Arg Cys Asp 8535 8540 8545 AAC AAT CGC TGC ATT TAT AGTCAT GAG GTG TGC AAT GGT GTG GAT GAC 11828 Asn Asn Arg Cys Ile Tyr SerHis Glu Val Cys Asn Gly Val Asp Asp 8550 8555 8560 TGT GGA GAT GGA ACTGAT GAG ACA GAG GAG CAC TGT AGA AAA CCG ACC 11876 Cys Gly Asp Gly ThrAsp Glu Thr Glu Glu His Cys Arg Lys Pro Thr 8565 8570 8575 8580 CCT AAACCT TGT ACA GAA TAT GAA TAT AAG TGT GGC AAT GGG CAT TGC 11924 Pro LysPro Cys Thr Glu Tyr Glu Tyr Lys Cys Gly Asn Gly His Cys 8585 8590 8595ATT CCA CAT GAC AAT GTG TGT GAT GAT GCC GAT GAC TGT GGT GAC TGG 11972Ile Pro His Asp Asn Val Cys Asp Asp Ala Asp Asp Cys Gly Asp Trp 86008605 8610 TCC GAT GAA CTG GGT TGC AAT AAA GGA AAA GAA AGA ACA TGT GCTGAA 12020 Ser Asp Glu Leu Gly Cys Asn Lys Gly Lys Glu Arg Thr Cys AlaGlu 8615 8620 8625 AAT ATA TGC GAG CAA AAT TGT ACC CAA TTA AAT GAA GGAGGA TTT ATC 12068 Asn Ile Cys Glu Gln Asn Cys Thr Gln Leu Asn Glu GlyGly Phe Ile 8630 8635 8640 TGC TCC TGT ACA GCT GGG TTC GAA ACC AAT GTTTTT GAC AGA ACC TCC 12116 Cys Ser Cys Thr Ala Gly Phe Glu Thr Asn ValPhe Asp Arg Thr Ser 8645 8650 8655 8660 TGT CTA GAT ATC AAT GAA TGT GAACAA TTT GGG ACT TGT CCC CAG CAC 12164 Cys Leu Asp Ile Asn Glu Cys GluGln Phe Gly Thr Cys Pro Gln His 8665 8670 8675 TGC AGA AAT ACC AAA GGAAGT TAT GAG TGT GTC TGT GCT GAT GGC TTC 12212 Cys Arg Asn Thr Lys GlySer Tyr Glu Cys Val Cys Ala Asp Gly Phe 8680 8685 8690 ACG TCT ATG AGTGAC CGC CCT GGA AAA CGA TGT GCA GCT GAG GGT AGC 12260 Thr Ser Met SerAsp Arg Pro Gly Lys Arg Cys Ala Ala Glu Gly Ser 8695 8700 8705 TCT CCTTTG TTG CTA CTG CCT GAC AAT GTC CGA ATT CGA AAA TAT AAT 12308 Ser ProLeu Leu Leu Leu Pro Asp Asn Val Arg Ile Arg Lys Tyr Asn 8710 8715 8720CTC TCA TCT GAG AGG TTC TCA GAG TAT CTT CAA GAT GAG GAA TAT ATC 12356Leu Ser Ser Glu Arg Phe Ser Glu Tyr Leu Gln Asp Glu Glu Tyr Ile 87258730 8735 8740 CAA GCT GTT GAT TAT GAT TGG GAT CCC GAG GAC ATA GGC CTCAGT GTT 12404 Gln Ala Val Asp Tyr Asp Trp Asp Pro Glu Asp Ile Gly LeuSer Val 8745 8750 8755 GTG TAT TAC ACT GTG CGA GGG GAG GGC TCT AGG TTTGGT GCT ATC AAA 12452 Val Tyr Tyr Thr Val Arg Gly Glu Gly Ser Arg PheGly Ala Ile Lys 8760 8765 8770 CGT GCC TAC ATC CCC AAC TTT GAA TCC GGCCGC AAT AAT CTT GTG CAG 12500 Arg Ala Tyr Ile Pro Asn Phe Glu Ser GlyArg Asn Asn Leu Val Gln 8775 8780 8785 GAA GTT GAC CTG AAA CTG AAA TACGTA ATG CAG CCA GAT GGA ATA GCA 12548 Glu Val Asp Leu Lys Leu Lys TyrVal Met Gln Pro Asp Gly Ile Ala 8790 8795 8800 GTG GAC TGG GTT GGA AGGCAT ATT TAC TGG TCA GAT GTC AAG AAT AAA 12596 Val Asp Trp Val Gly ArgHis Ile Tyr Trp Ser Asp Val Lys Asn Lys 8805 8810 8815 8820 CGC ATT GAGGTG GCT AAA CTT GAT GGA AGG TAC AGA AAG TGG CTG ATT 12644 Arg Ile GluVal Ala Lys Leu Asp Gly Arg Tyr Arg Lys Trp Leu Ile 8825 8830 8835 TCCACT GAC CTG GAC CAA CCA GCT GCT ATT GCT GTG AAT CCC AAA CTA 12692 SerThr Asp Leu Asp Gln Pro Ala Ala Ile Ala Val Asn Pro Lys Leu 8840 88458850 GGG CTT ATG TTC TGG ACT GAC TGG GGA AAG GAA CCT AAA MTC GAG TCT12740 Gly Leu Met Phe Trp Thr Asp Trp Gly Lys Glu Pro Lys Xaa Glu Ser8855 8860 8865 GCC TGG ATG AAT GGA GAG GAC CGC AAC ATC CTG GTT TTC GAGGAC CTT 12788 Ala Trp Met Asn Gly Glu Asp Arg Asn Ile Leu Val Phe GluAsp Leu 8870 8875 8880 GGT TGG CCA ACT GGC CTT TCT ATC GAT TAT TTG AACAAT GAC CGA ATC 12836 Gly Trp Pro Thr Gly Leu Ser Ile Asp Tyr Leu AsnAsn Asp Arg Ile 8885 8890 8895 8900 TAC TGG AGT GAC TTC AAG GAG GAC GTTATT GAA ACC ATA AAA TAT GAT 12884 Tyr Trp Ser Asp Phe Lys Glu Asp ValIle Glu Thr Ile Lys Tyr Asp 8905 8910 8915 GGG ACT GAT AGG AGA GTC ATTGCA AAG GAA GCA ATG AAC CCT TAC AGC 12932 Gly Thr Asp Arg Arg Val IleAla Lys Glu Ala Met Asn Pro Tyr Ser 8920 8925 8930 CTG GAC ATC TTT GAAGAC CAG TTA TAC TGG ATA TCT AAG GAA AAG GGA 12980 Leu Asp Ile Phe GluAsp Gln Leu Tyr Trp Ile Ser Lys Glu Lys Gly 8935 8940 8945 GAA GTA TGGAAA CAA AAT AAA TTT GGG CAA GGA AAG AAA GAG AAA ACG 13028 Glu Val TrpLys Gln Asn Lys Phe Gly Gln Gly Lys Lys Glu Lys Thr 8950 8955 8960 CTGGTA GTG AAC CCT TGG CTC ACT CAA GTT CGA ATC TTT CAT CAA CTC 13076 LeuVal Val Asn Pro Trp Leu Thr Gln Val Arg Ile Phe His Gln Leu 8965 89708975 8980 AGA TAC AAT AAG TCA GTG CCC AAC CTT TGC AAA CAG ATC TGC AGCCAC 13124 Arg Tyr Asn Lys Ser Val Pro Asn Leu Cys Lys Gln Ile Cys SerHis 8985 8990 8995 CTC TGC CTT CTG AGA CCT GGA GGA TAC AGC TGT GCC TGTCCC CAA GGC 13172 Leu Cys Leu Leu Arg Pro Gly Gly Tyr Ser Cys Ala CysPro Gln Gly 9000 9005 9010 TCC AGC TTT ATA GAG GGG AGC ACC ACT GAG TGTGAT GCA GCC ATC GAA 13220 Ser Ser Phe Ile Glu Gly Ser Thr Thr Glu CysAsp Ala Ala Ile Glu 9015 9020 9025 CTG CCT ATC AAC CTG CCC CCC CCA TGCAGG TGC ATG CAC GGA GGA AAT 13268 Leu Pro Ile Asn Leu Pro Pro Pro CysArg Cys Met His Gly Gly Asn 9030 9035 9040 TGC TAT TTT GAT GAG ACT GACCTC CCC AAA TGC AAG TGT CCT AGC GGC 13316 Cys Tyr Phe Asp Glu Thr AspLeu Pro Lys Cys Lys Cys Pro Ser Gly 9045 9050 9055 9060 TAC ACC GGA AAATAT TGT GAA ATG GCG TTT TCA AAA GGC ATC TCT CCA 13364 Tyr Thr Gly LysTyr Cys Glu Met Ala Phe Ser Lys Gly Ile Ser Pro 9065 9070 9075 GGA ACAACC GCA GTA GCT GTG CTG TTG ACA ATC CTC TTG ATC GTC GTA 13412 Gly ThrThr Ala Val Ala Val Leu Leu Thr Ile Leu Leu Ile Val Val 9080 9085 9090ATT GGA GCT CTG GCA ATT GCA GGA TTC TTC CAC TAT AGA AGG ACC GGC 13460Ile Gly Ala Leu Ala Ile Ala Gly Phe Phe His Tyr Arg Arg Thr Gly 90959100 9105 TCC CTT TTG CCT GCT CTG CCC AAG CTG CCA AGC TTA AGC AGT CTCGTC 13508 Ser Leu Leu Pro Ala Leu Pro Lys Leu Pro Ser Leu Ser Ser LeuVal 9110 9115 9120 AAG CCC TCT GAA AAT GGG AAT GGG GTG ACC TTC AGA TCAGGG GCA GAT 13556 Lys Pro Ser Glu Asn Gly Asn Gly Val Thr Phe Arg SerGly Ala Asp 9125 9130 9135 9140 CTT AAC ATG GAT ATT GGA GTG TCT GGT TTTGGA CCT GAG ACT GCT ATT 13604 Leu Asn Met Asp Ile Gly Val Ser Gly PheGly Pro Glu Thr Ala Ile 9145 9150 9155 GAC AGG TCA ATG GCA ATG AGT GAAGAC TTT GTC ATG GAA ATG GGG AAG 13652 Asp Arg Ser Met Ala Met Ser GluAsp Phe Val Met Glu Met Gly Lys 9160 9165 9170 CAG CCC ATA ATA TTT GAAAAC CCA ATG TAC TCA GCC AGA GAC AGT GCT 13700 Gln Pro Ile Ile Phe GluAsn Pro Met Tyr Ser Ala Arg Asp Ser Ala 9175 9180 9185 GTC AAA GTG GTTCAG CCA ATC CAG GTG ACT GTA TCT GAA AAT GTG GAT 13748 Val Lys Val ValGln Pro Ile Gln Val Thr Val Ser Glu Asn Val Asp 9190 9195 9200 AAT AAGAAT TAT GGA AGT CCC ATA AAC CCT TCT GAG ATA GTT CCA GAG 13796 Asn LysAsn Tyr Gly Ser Pro Ile Asn Pro Ser Glu Ile Val Pro Glu 9205 9210 92159220 ACA AAC CCA ACT TCA CCA GCT GCT GAT GGA ACT CAG GTG ACA AAA TGG13844 Thr Asn Pro Thr Ser Pro Ala Ala Asp Gly Thr Gln Val Thr Lys Trp9225 9230 9235 AAT CTC TTC AAA CGA AAA TCT AAA CAA ACT ACC AAC TTT GAAAAT CCA 13892 Asn Leu Phe Lys Arg Lys Ser Lys Gln Thr Thr Asn Phe GluAsn Pro 9240 9245 9250 ATC TAT GCA CAG ATG GAG AAC GAG CAA AAG GAA AGTGTT GCT GCG ACA 13940 Ile Tyr Ala Gln Met Glu Asn Glu Gln Lys Glu SerVal Ala Ala Thr 9255 9260 9265 CCA CCT CCA TCA CCT TCG CTC CCT GCT AAGCCT AAG CCT CCT TCG AGA 13988 Pro Pro Pro Ser Pro Ser Leu Pro Ala LysPro Lys Pro Pro Ser Arg 9270 9275 9280 AGA GAC CCA ACT CCA ACC TAT TCTGCA ACA GAA GAC ACT TTT AAA GAC 14036 Arg Asp Pro Thr Pro Thr Tyr SerAla Thr Glu Asp Thr Phe Lys Asp 9285 9290 9295 9300 ACC GCA AAT CTT GTTAAA GAA GAC TCT GAA GTA TAG CTATACCA 14080 Thr Ala Asn Leu Val Lys GluAsp Ser Glu Val * 9305 9310 4655 amino acids amino acid linear proteinunknown 88 Met Asp Arg Gly Pro Ala Ala Val Ala Cys Thr Leu Leu Leu AlaLeu 1 5 10 15 Val Ala Cys Leu Ala Pro Ala Ser Gly Gln Glu Cys Asp SerAla His 20 25 30 Phe Arg Cys Gly Ser Gly His Cys Ile Pro Ala Asp Trp ArgCys Asp 35 40 45 Gly Thr Lys Asp Cys Ser Asp Asp Ala Asp Glu Ile Gly CysAla Val 50 55 60 Val Thr Cys Gln Gln Gly Tyr Phe Lys Cys Gln Ser Glu GlyGln Cys 65 70 75 80 Ile Pro Ser Ser Trp Val Cys Asp Gln Asp Gln Asp CysAsp Asp Gly 85 90 95 Ser Asp Glu Arg Gln Asp Cys Ser Gln Ser Thr Cys SerSer His Gln 100 105 110 Ile Thr Cys Ser Asn Gly Gln Cys Ile Pro Ser GluTyr Arg Cys Asp 115 120 125 His Val Arg Asp Cys Pro Asp Gly Ala Asp GluAsn Asp Cys Gln Tyr 130 135 140 Pro Thr Cys Glu Gln Leu Thr Cys Asp AsnGly Ala Cys Tyr Asn Thr 145 150 155 160 Ser Gln Lys Cys Asp Trp Lys ValAsp Cys Arg Asp Ser Ser Asp Glu 165 170 175 Ile Asn Cys Thr Glu Ile CysLeu His Asn Glu Phe Ser Cys Gly Asn 180 185 190 Gly Glu Cys Ile Pro ArgAla Tyr Val Cys Asp His Asp Asn Asp Cys 195 200 205 Gln Asp Gly Ser AspGlu His Ala Cys Asn Tyr Pro Thr Cys Gly Gly 210 215 220 Tyr Gln Phe ThrCys Pro Ser Gly Arg Cys Ile Tyr Gln Asn Trp Val 225 230 235 240 Cys AspGly Glu Asp Asp Cys Lys Asp Asn Gly Asp Glu Asp Gly Cys 245 250 255 GluSer Gly Pro His Asp Val His Lys Cys Ser Pro Arg Glu Trp Ser 260 265 270Cys Pro Glu Ser Gly Arg Cys Ile Ser Ile Tyr Lys Val Cys Asp Gly 275 280285 Ile Leu Asp Cys Pro Gly Arg Glu Asp Glu Asn Asn Thr Ser Thr Gly 290295 300 Lys Tyr Cys Ser Met Thr Leu Cys Ser Ala Leu Asn Cys Gln Tyr Gln305 310 315 320 Cys His Glu Thr Pro Tyr Gly Gly Ala Cys Phe Cys Pro ProGly Tyr 325 330 335 Ile Ile Asn His Asn Asp Ser Arg Thr Cys Val Glu PheAsp Asp Cys 340 345 350 Gln Ile Trp Gly Ile Cys Asp Gln Lys Cys Glu SerArg Pro Gly Arg 355 360 365 His Leu Cys His Cys Glu Glu Gly Tyr Ile LeuGlu Arg Gly Gln Tyr 370 375 380 Cys Lys Ala Asn Asp Ser Phe Gly Glu AlaSer Ile Ile Phe Ser Asn 385 390 395 400 Gly Arg Asp Leu Leu Ile Gly AspIle His Gly Arg Ser Phe Arg Ile 405 410 415 Leu Val Glu Ser Gln Asn ArgGly Val Ala Val Gly Val Ala Phe His 420 425 430 Tyr His Leu Gln Arg ValPhe Trp Thr Asp Thr Val Gln Asn Lys Val 435 440 445 Phe Ser Val Asp IleAsn Gly Leu Asn Ile Gln Glu Val Leu Asn Val 450 455 460 Ser Val Glu ThrPro Glu Asn Leu Ala Val Asp Trp Val Asn Asn Lys 465 470 475 480 Ile TyrLeu Val Glu Thr Lys Val Asn Arg Ile Asp Met Val Asn Leu 485 490 495 AspGly Ser Tyr Arg Val Thr Leu Ile Thr Glu Asn Leu Gly His Pro 500 505 510Arg Gly Ile Ala Val Asp Pro Thr Val Gly Tyr Leu Phe Phe Ser Asp 515 520525 Trp Glu Ser Leu Ser Gly Glu Pro Lys Leu Glu Arg Ala Phe Met Asp 530535 540 Gly Ser Asn Arg Lys Asp Leu Val Lys Thr Lys Leu Gly Trp Pro Ala545 550 555 560 Gly Val Thr Leu Asp Met Ile Ser Lys Arg Val Tyr Trp ValAsp Ser 565 570 575 Arg Phe Asp Tyr Ile Glu Thr Val Thr Tyr Asp Gly IleGln Arg Lys 580 585 590 Thr Val Val His Gly Gly Ser Leu Ile Pro His ProPhe Gly Val Ser 595 600 605 Leu Phe Glu Gly Gln Val Phe Phe Thr Asp TrpThr Lys Met Ala Val 610 615 620 Leu Lys Ala Asn Lys Phe Thr Glu Thr AsnPro Gln Val Tyr Tyr Gln 625 630 635 640 Ala Ser Leu Arg Pro Tyr Gly ValThr Val Tyr His Ser Leu Arg Gln 645 650 655 Pro Tyr Ala Thr Asn Pro CysLys Asp Asn Asn Gly Gly Cys Glu Gln 660 665 670 Val Cys Val Leu Ser HisArg Thr Asp Asn Asp Gly Leu Gly Phe Arg 675 680 685 Cys Lys Cys Thr PheGly Phe Gln Leu Asp Thr Asp Glu Arg His Cys 690 695 700 Ile Ala Val GlnAsn Phe Leu Ile Phe Ser Ser Gln Val Ala Ile Arg 705 710 715 720 Gly IlePro Phe Thr Leu Ser Thr Gln Glu Asp Val Met Val Pro Val 725 730 735 SerGly Asn Pro Ser Phe Phe Val Gly Ile Asp Phe Asp Ala Gln Asp 740 745 750Ser Thr Ile Phe Phe Ser Asp Met Ser Lys His Met Ile Phe Lys Gln 755 760765 Lys Ile Asp Gly Thr Gly Arg Glu Ile Leu Ala Ala Asn Arg Val Glu 770775 780 Asn Val Glu Ser Leu Ala Phe Asp Trp Ile Ser Lys Asn Leu Tyr Trp785 790 795 800 Thr Asp Ser His Tyr Lys Ser Ile Ser Val Met Arg Leu AlaAsp Lys 805 810 815 Thr Arg Arg Thr Val Val Gln Tyr Leu Asn Asn Pro ArgSer Val Val 820 825 830 Val His Pro Phe Ala Gly Tyr Leu Phe Phe Thr AspTrp Phe Arg Pro 835 840 845 Ala Lys Ile Met Arg Ala Trp Ser Asp Gly SerHis Leu Leu Pro Val 850 855 860 Ile Asn Thr Thr Leu Gly Trp Pro Asn GlyLeu Ala Ile Asp Trp Ala 865 870 875 880 Ala Ser Arg Leu Tyr Trp Val AspAla Tyr Phe Asp Lys Ile Glu His 885 890 895 Ser Thr Phe Asp Gly Leu AspArg Arg Arg Leu Gly His Ile Glu Gln 900 905 910 Met Thr His Pro Phe GlyLeu Ala Ile Phe Gly Glu His Leu Phe Phe 915 920 925 Thr Asp Trp Arg LeuGly Ala Ile Ile Arg Val Arg Lys Ala Asp Gly 930 935 940 Gly Glu Met ThrVal Ile Arg Ser Gly Ile Ala Tyr Ile Leu His Leu 945 950 955 960 Lys SerTyr Asp Val Asn Ile Gln Thr Gly Ser Asn Ala Cys Asn Gln 965 970 975 ProThr His Pro Asn Gly Asp Cys Ser His Phe Cys Phe Pro Val Pro 980 985 990Asn Phe Gln Arg Val Cys Gly Cys Pro Tyr Gly Met Arg Leu Ala Ser 995 10001005 Asn His Leu Thr Cys Glu Gly Asp Pro Thr Asn Glu Pro Pro Thr Glu1010 1015 1020 Gln Cys Gly Leu Phe Ser Phe Pro Cys Lys Asn Gly Arg CysVal Pro 1025 1030 1035 1040 Asn Tyr Tyr Leu Cys Asp Gly Val Asp Asp CysHis Asp Asn Ser Asp 1045 1050 1055 Glu Gln Leu Cys Gly Thr Leu Asn AsnThr Cys Ser Ser Ser Ala Phe 1060 1065 1070 Thr Cys Gly His Gly Glu CysIle Pro Ala His Trp Arg Cys Asp Lys 1075 1080 1085 Arg Asn Asp Cys ValAsp Gly Ser Asp Glu His Asn Cys Pro Thr His 1090 1095 1100 Ala Pro AlaSer Cys Leu Asp Thr Gln Tyr Thr Cys Asp Asn His Gln 1105 1110 1115 1120Cys Ile Ser Lys Asn Trp Val Cys Asp Thr Asp Asn Asp Cys Gly Asp 11251130 1135 Gly Ser Asp Glu Lys Asn Cys Asn Ser Thr Glu Thr Cys Gln ProSer 1140 1145 1150 Gln Phe Asn Cys Pro Asn His Arg Cys Ile Asp Leu SerPhe Val Cys 1155 1160 1165 Asp Gly Asp Lys Asp Cys Val Asp Gly Ser AspGlu Val Gly Cys Val 1170 1175 1180 Leu Asn Cys Thr Ala Ser Gln Phe LysCys Ala Ser Gly Asp Lys Cys 1185 1190 1195 1200 Ile Gly Val Thr Asn ArgCys Asp Gly Val Phe Asp Cys Ser Asp Asn 1205 1210 1215 Ser Asp Glu AlaGly Cys Pro Thr Arg Pro Pro Gly Met Cys His Ser 1220 1225 1230 Asp GluPhe Gln Cys Gln Glu Asp Gly Ile Cys Ile Pro Asn Phe Trp 1235 1240 1245Glu Cys Asp Gly His Pro Asp Cys Leu Tyr Gly Ser Asp Glu His Asn 12501255 1260 Ala Cys Val Pro Lys Thr Cys Pro Ser Ser Tyr Phe His Cys AspAsn 1265 1270 1275 1280 Gly Asn Cys Ile His Arg Ala Trp Leu Cys Asp ArgAsp Asn Asp Cys 1285 1290 1295 Gly Asp Met Ser Asp Glu Lys Asp Cys ProThr Gln Pro Phe Arg Cys 1300 1305 1310 Pro Ser Trp Gln Trp Gln Cys LeuGly His Asn Ile Cys Val Asn Leu 1315 1320 1325 Ser Val Val Cys Asp GlyIle Phe Asp Cys Pro Asn Gly Thr Asp Glu 1330 1335 1340 Ser Pro Leu CysAsn Gly Asn Ser Cys Ser Asp Phe Asn Gly Gly Cys 1345 1350 1355 1360 ThrHis Glu Cys Val Gln Glu Pro Phe Gly Ala Lys Cys Leu Cys Pro 1365 13701375 Leu Gly Phe Leu Leu Ala Asn Asp Ser Lys Thr Cys Glu Asp Ile Asp1380 1385 1390 Glu Cys Asp Ile Leu Gly Ser Cys Ser Gln His Cys Tyr AsnMet Arg 1395 1400 1405 Gly Ser Phe Arg Cys Ser Cys Asp Thr Gly Tyr MetLeu Glu Ser Asp 1410 1415 1420 Gly Arg Thr Cys Lys Val Thr Ala Ser GluSer Leu Leu Leu Leu Val 1425 1430 1435 1440 Ala Ser Gln Asn Lys Ile IleAla Asp Ser Val Thr Ser Gln Val His 1445 1450 1455 Asn Ile Tyr Ser LeuVal Glu Asn Gly Ser Tyr Ile Val Ala Val Asp 1460 1465 1470 Phe Asp SerIle Ser Gly Arg Ile Phe Trp Ser Asp Ala Thr Gln Gly 1475 1480 1485 LysThr Trp Ser Ala Phe Gln Asn Gly Thr Asp Arg Arg Val Val Phe 1490 14951500 Asp Ser Ser Ile Ile Leu Thr Glu Thr Ile Ala Ile Asp Trp Val Gly1505 1510 1515 1520 Arg Asn Leu Tyr Trp Thr Asp Tyr Ala Leu Glu Thr IleGlu Val Ser 1525 1530 1535 Lys Ile Asp Gly Ser His Arg Thr Val Leu IleSer Lys Asn Leu Thr 1540 1545 1550 Asn Pro Arg Gly Leu Ala Leu Asp ProArg Met Asn Glu His Leu Leu 1555 1560 1565 Phe Trp Ser Asp Trp Gly HisHis Pro Arg Ile Glu Arg Ala Ser Met 1570 1575 1580 Asp Gly Ser Met ArgThr Val Ile Val Gln Asp Lys Ile Phe Trp Pro 1585 1590 1595 1600 Cys GlyLeu Thr Ile Asp Tyr Pro Asn Arg Leu Leu Tyr Phe Met Asp 1605 1610 1615Ser Tyr Leu Asp Tyr Met Asp Phe Cys Asp Tyr Asn Gly His His Arg 16201625 1630 Arg Gln Val Ile Ala Ser Asp Leu Ile Ile Arg His Pro Tyr AlaLeu 1635 1640 1645 Thr Leu Phe Glu Asp Ser Val Tyr Trp Thr Asp Arg AlaThr Arg Arg 1650 1655 1660 Val Met Arg Ala Asn Lys Trp His Gly Gly AsnGln Ser Val Val Met 1665 1670 1675 1680 Tyr Asn Ile Gln Trp Pro Leu GlyIle Val Ala Val His Pro Ser Lys 1685 1690 1695 Gln Pro Asn Ser Val AsnPro Cys Ala Phe Ser Arg Cys Ser His Leu 1700 1705 1710 Cys Leu Leu SerSer Gln Gly Pro His Phe Tyr Ser Cys Val Cys Pro 1715 1720 1725 Ser GlyTrp Ser Leu Ser Pro Asp Leu Leu Asn Cys Leu Arg Asp Asp 1730 1735 1740Gln Pro Phe Leu Ile Thr Val Arg Gln His Ile Ile Phe Gly Ile Ser 17451750 1755 1760 Leu Asn Pro Glu Val Lys Ser Asn Asp Ala Met Val Pro IleAla Gly 1765 1770 1775 Ile Gln Asn Gly Leu Asp Val Glu Phe Asp Asp AlaGlu Gln Tyr Ile 1780 1785 1790 Tyr Trp Val Glu Asn Pro Gly Glu Ile HisArg Val Lys Thr Asp Gly 1795 1800 1805 Thr Asn Arg Thr Val Phe Ala SerIle Ser Met Val Gly Pro Ser Met 1810 1815 1820 Asn Leu Ala Leu Asp TrpIle Ser Arg Asn Leu Tyr Ser Thr Asn Pro 1825 1830 1835 1840 Arg Thr GlnSer Ile Glu Val Leu Thr Leu His Gly Asp Ile Arg Tyr 1845 1850 1855 ArgLys Thr Leu Ile Ala Asn Asp Gly Thr Ala Leu Gly Val Gly Phe 1860 18651870 Pro Ile Gly Ile Thr Val Asp Pro Ala Arg Gly Lys Leu Tyr Trp Ser1875 1880 1885 Asp Gln Gly Thr Asp Ser Gly Val Pro Ala Lys Ile Ala SerAla Asn 1890 1895 1900 Met Asp Gly Thr Ser Val Lys Thr Leu Phe Thr GlyAsn Leu Glu His 1905 1910 1915 1920 Leu Glu Cys Val Thr Leu Asp Ile GluGlu Gln Lys Leu Tyr Trp Ala 1925 1930 1935 Val Thr Gly Arg Gly Val IleGlu Arg Gly Asn Val Asp Gly Thr Asp 1940 1945 1950 Arg Met Ile Leu ValHis Gln Leu Ser His Pro Trp Gly Ile Ala Val 1955 1960 1965 His Asp SerPhe Leu Tyr Tyr Thr Asp Glu Gln Tyr Glu Val Ile Glu 1970 1975 1980 ArgVal Asp Lys Ala Thr Gly Ala Asn Lys Ile Val Leu Arg Asp Asn 1985 19901995 2000 Val Pro Asn Leu Arg Gly Leu Gln Val Tyr His Arg Arg Asn AlaAla 2005 2010 2015 Glu Ser Ser Asn Gly Cys Ser Asn Asn Met Asn Ala CysGln Gln Ile 2020 2025 2030 Cys Leu Pro Val Pro Gly Gly Leu Phe Ser CysAla Cys Ala Thr Gly 2035 2040 2045 Phe Lys Leu Asn Pro Asp Asn Arg SerCys Ser Pro Tyr Asn Ser Phe 2050 2055 2060 Ile Val Val Ser Met Leu SerAla Ile Arg Gly Phe Ser Leu Glu Leu 2065 2070 2075 2080 Ser Asp His SerGlu Thr Met Val Pro Val Ala Gly Gln Gly Arg Asn 2085 2090 2095 Ala LeuHis Val Asp Val Asp Val Ser Ser Gly Phe Ile Tyr Trp Cys 2100 2105 2110Asp Phe Ser Ser Ser Val Ala Ser Asp Asn Ala Ile Arg Arg Ile Lys 21152120 2125 Pro Asp Gly Ser Ser Leu Met Asn Ile Val Thr His Gly Ile GlyGlu 2130 2135 2140 Asn Gly Val Arg Gly Ile Ala Val Asp Trp Val Ala GlyAsn Leu Tyr 2145 2150 2155 2160 Phe Thr Asn Ala Phe Val Ser Glu Thr LeuIle Glu Val Leu Arg Ile 2165 2170 2175 Asn Thr Thr Tyr Arg Arg Val LeuLeu Lys Val Thr Val Asp Met Pro 2180 2185 2190 Arg His Ile Val Val AspPro Lys Asn Arg Tyr Leu Phe Trp Ala Asp 2195 2200 2205 Tyr Gly Gln ArgPro Lys Ile Glu Arg Ser Phe Leu Asp Cys Thr Asn 2210 2215 2220 Arg ThrVal Leu Val Ser Glu Gly Ile Val Thr Pro Arg Gly Leu Ala 2225 2230 22352240 Val Asp Arg Ser Asp Gly Tyr Val Tyr Trp Val Asp Asp Ser Leu Asp2245 2250 2255 Ile Ile Ala Arg Ile Arg Ile Asn Gly Glu Asn Ser Glu ValIle Arg 2260 2265 2270 Tyr Gly Ser Arg Tyr Pro Thr Pro Tyr Gly Ile ThrVal Phe Glu Asn 2275 2280 2285 Ser Ile Ile Trp Val Asp Arg Asn Leu LysLys Ile Phe Gln Ala Ser 2290 2295 2300 Lys Glu Pro Glu Asn Thr Glu ProPro Thr Val Ile Arg Asp Asn Ile 2305 2310 2315 2320 Asn Trp Leu Arg AspVal Thr Ile Phe Asp Lys Gln Val Gln Pro Arg 2325 2330 2335 Ser Pro AlaGlu Val Asn Asn Asn Pro Cys Leu Glu Asn Asn Gly Gly 2340 2345 2350 CysSer His Leu Cys Phe Ala Leu Pro Gly Leu His Thr Pro Lys Cys 2355 23602365 Asp Cys Ala Phe Gly Thr Leu Gln Ser Asp Gly Lys Asn Cys Ala Ile2370 2375 2380 Ser Thr Glu Asn Phe Leu Ile Phe Ala Leu Ser Asn Ser LeuArg Ser 2385 2390 2395 2400 Leu His Leu Asp Pro Glu Asn His Ser Pro ProPhe Gln Thr Ile Asn 2405 2410 2415 Val Glu Arg Thr Val Met Ser Leu AspTyr Asp Ser Val Ser Asp Arg 2420 2425 2430 Ile Tyr Phe Thr Gln Asn LeuAla Ser Gly Val Gly Gln Ile Ser Tyr 2435 2440 2445 Ala Thr Leu Ser SerGly Ile His Thr Pro Thr Val Ile Ala Ser Gly 2450 2455 2460 Ile Gly ThrAla Asp Gly Ile Ala Phe Asp Trp Ile Thr Arg Arg Ile 2465 2470 2475 2480Tyr Tyr Ser Asp Tyr Leu Asn Gln Met Ile Asn Ser Met Ala Glu Asp 24852490 2495 Gly Ser Asn Arg Thr Val Ile Ala Arg Val Pro Lys Pro Arg AlaIle 2500 2505 2510 Val Leu Asp Pro Cys Gln Gly Tyr Leu Tyr Trp Ala AspTrp Asp Thr 2515 2520 2525 His Ala Lys Ile Glu Arg Ala Thr Leu Gly GlyAsn Phe Arg Val Pro 2530 2535 2540 Ile Val Asn Ser Ser Leu Val Met ProSer Gly Leu Thr Leu Asp Tyr 2545 2550 2555 2560 Glu Glu Asp Leu Leu TyrTrp Val Asp Ala Ser Leu Gln Arg Ile Glu 2565 2570 2575 Arg Ser Thr LeuThr Gly Val Asp Arg Glu Val Ile Val Asn Ala Ala 2580 2585 2590 Val HisAla Phe Gly Leu Thr Leu Tyr Gly Gln Tyr Ile Tyr Trp Thr 2595 2600 2605Asp Leu Tyr Thr Gln Arg Ile Tyr Arg Ala Asn Lys Tyr Asp Gly Ser 26102615 2620 Gly Gln Ile Ala Met Thr Thr Asn Leu Leu Ser Gln Pro Arg GlyIle 2625 2630 2635 2640 Asn Thr Val Val Lys Asn Gln Lys Gln Gln Cys AsnAsn Pro Cys Glu 2645 2650 2655 Gln Phe Asn Gly Gly Cys Ser His Ile CysAla Pro Gly Pro Asn Gly 2660 2665 2670 Ala Glu Cys Gln Cys Pro His GluGly Asn Trp Tyr Leu Ala Asn Asn 2675 2680 2685 Arg Lys His Cys Ile ValAsp Asn Gly Glu Arg Cys Gly Ala Ser Ser 2690 2695 2700 Phe Thr Cys SerAsn Gly Arg Cys Ile Ser Glu Glu Trp Lys Cys Asp 2705 2710 2715 2720 AsnAsp Asn Asp Cys Gly Asp Gly Ser Asp Glu Met Glu Ser Val Cys 2725 27302735 Ala Leu His Thr Cys Ser Pro Thr Ala Phe Thr Cys Ala Asn Gly Arg2740 2745 2750 Cys Val Gln Tyr Ser Tyr Arg Cys Asp Tyr Tyr Asn Asp CysGly Asp 2755 2760 2765 Gly Ser Asp Glu Ala Gly Cys Leu Phe Arg Asp CysAsn Ala Thr Thr 2770 2775 2780 Glu Phe Met Cys Asn Asn Arg Arg Cys IlePro Arg Glu Phe Ile Cys 2785 2790 2795 2800 Asn Gly Val Asp Asn Cys HisAsp Asn Asn Thr Ser Asp Glu Lys Asn 2805 2810 2815 Cys Pro Asp Arg ThrCys Gln Ser Gly Tyr Thr Lys Cys His Asn Ser 2820 2825 2830 Asn Ile CysIle Pro Arg Val Tyr Leu Cys Asp Gly Asp Asn Asp Cys 2835 2840 2845 GlyAsp Asn Ser Asp Glu Asn Pro Thr Tyr Cys Thr Thr His Thr Cys 2850 28552860 Ser Ser Ser Glu Phe Gln Cys Ala Ser Gly Arg Cys Ile Pro Gln His2865 2870 2875 2880 Trp Tyr Cys Asp Gln Glu Thr Asp Cys Phe Asp Ala SerAsp Glu Pro 2885 2890 2895 Ala Ser Cys Gly His Ser Glu Arg Thr Cys LeuAla Asp Glu Phe Lys 2900 2905 2910 Cys Asp Gly Gly Arg Cys Ile Pro SerGlu Trp Ile Cys Asp Gly Asp 2915 2920 2925 Asn Asp Cys Gly Asp Met SerAsp Glu Asp Lys Arg His Gln Cys Gln 2930 2935 2940 Asn Gln Asn Cys SerAsp Ser Glu Phe Leu Cys Val Asn Asp Arg Pro 2945 2950 2955 2960 Pro AspArg Arg Cys Ile Pro Gln Ser Trp Val Cys Asp Gly Asp Val 2965 2970 2975Asp Cys Thr Asp Gly Tyr Asp Glu Asn Gln Asn Cys Thr Arg Arg Thr 29802985 2990 Cys Ser Glu Asn Glu Phe Thr Cys Gly Tyr Gly Leu Cys Ile ProLys 2995 3000 3005 Ile Phe Arg Cys Asp Arg His Asn Asp Cys Gly Asp TyrSer Asp Glu 3010 3015 3020 Arg Gly Cys Leu Tyr Gln Thr Cys Gln Gln AsnGln Phe Thr Cys Gln 3025 3030 3035 3040 Asn Gly Arg Cys Ile Ser Lys ThrPhe Val Cys Asp Glu Asp Asn Asp 3045 3050 3055 Cys Gly Asp Gly Ser AspGlu Leu Met His Leu Cys His Thr Pro Glu 3060 3065 3070 Pro Thr Cys ProPro His Glu Phe Lys Cys Asp Asn Gly Arg Cys Ile 3075 3080 3085 Glu MetMet Lys Leu Cys Asn His Leu Asp Asp Cys Leu Asp Asn Ser 3090 3095 3100Asp Glu Lys Gly Cys Gly Ile Asn Glu Cys His Asp Pro Ser Ile Ser 31053110 3115 3120 Gly Cys Asp His Asn Cys Thr Asp Thr Leu Thr Ser Phe TyrCys Ser 3125 3130 3135 Cys Arg Pro Gly Tyr Lys Leu Met Ser Asp Lys ArgThr Cys Val Asp 3140 3145 3150 Ile Asp Glu Cys Thr Glu Met Pro Phe ValCys Ser Gln Lys Cys Glu 3155 3160 3165 Asn Val Ile Gly Ser Tyr Ile CysLys Cys Ala Pro Gly Tyr Leu Arg 3170 3175 3180 Glu Pro Asp Gly Lys ThrCys Arg Gln Asn Ser Asn Ile Glu Pro Tyr 3185 3190 3195 3200 Leu Ile PheSer Asn Arg Tyr Tyr Leu Arg Asn Leu Thr Ile Asp Gly 3205 3210 3215 TyrPhe Tyr Ser Leu Ile Leu Glu Gly Leu Asp Asn Val Val Ala Leu 3220 32253230 Asp Phe Asp Arg Val Glu Lys Arg Leu Tyr Trp Ile Asp Thr Gln Arg3235 3240 3245 Gln Val Ile Glu Arg Met Phe Leu Asn Lys Thr Asn Lys GluThr Ile 3250 3255 3260 Ile Asn His Arg Leu Pro Ala Ala Glu Ser Leu AlaVal Asp Trp Val 3265 3270 3275 3280 Ser Arg Lys Leu Tyr Trp Leu Asp AlaArg Leu Asp Gly Leu Phe Val 3285 3290 3295 Ser Asp Leu Asn Gly Gly HisArg Arg Met Leu Ala Gln His Cys Val 3300 3305 3310 Asp Ala Asn Asn ThrPhe Cys Phe Asp Asn Pro Arg Gly Leu Ala Leu 3315 3320 3325 His Pro GlnTyr Gly Tyr Leu Tyr Trp Ala Asp Trp Gly His Arg Ala 3330 3335 3340 TyrIle Gly Arg Val Gly Met Asp Gly Thr Asn Lys Ser Val Ile Ile 3345 33503355 3360 Ser Thr Lys Leu Glu Trp Pro Asn Gly Ile Thr Ile Asp Tyr ThrAsn 3365 3370 3375 Asp Leu Leu Tyr Trp Ala Asp Ala His Leu Gly Tyr IleGlu Tyr Ser 3380 3385 3390 Asp Leu Glu Gly His His Arg His Thr Val TyrAsp Gly Ala Leu Pro 3395 3400 3405 His Pro Phe Ala Ile Thr Ile Phe GluAsp Thr Ile Tyr Trp Thr Asp 3410 3415 3420 Trp Asn Thr Arg Thr Val GluLys Gly Asn Lys Tyr Asp Gly Ser Asn 3425 3430 3435 3440 Arg Gln Thr LeuVal Asn Thr Thr His Arg Pro Phe Asp Ile His Val 3445 3450 3455 Tyr HisPro Tyr Arg Gln Pro Ile Val Ser Asn Pro Cys Gly Thr Asn 3460 3465 3470Asn Gly Gly Cys Ser His Leu Cys Leu Ile Lys Pro Gly Gly Lys Gly 34753480 3485 Phe Thr Cys Glu Cys Pro Asp Asp Phe Arg Thr Leu Gln Leu SerGly 3490 3495 3500 Ser Thr Tyr Cys Met Pro Met Cys Ser Ser Thr Gln PheLeu Cys Ala 3505 3510 3515 3520 Asn Asn Glu Lys Cys Ile Pro Ile Trp TrpLys Cys Asp Gly Gln Lys 3525 3530 3535 Asp Cys Ser Asp Gly Ser Asp GluLeu Ala Leu Cys Pro Gln Arg Phe 3540 3545 3550 Cys Arg Leu Gly Gln PheGln Cys Ser Asp Gly Asn Cys Thr Ser Pro 3555 3560 3565 Gln Thr Leu CysAsn Ala His Gln Asn Cys Pro Asp Gly Ser Asp Glu 3570 3575 3580 Asp ArgLeu Leu Cys Glu Asn His His Cys Asp Ser Asn Glu Trp Gln 3585 3590 35953600 Cys Ala Asn Lys Arg Cys Ile Pro Glu Ser Trp Gln Cys Asp Thr Phe3605 3610 3615 Asn Asp Cys Glu Asp Asn Ser Asp Glu Asp Ser Ser His CysAla Ser 3620 3625 3630 Arg Thr Cys Arg Pro Gly Gln Phe Arg Cys Ala AsnGly Arg Cys Ile 3635 3640 3645 Pro Gln Ala Trp Lys Cys Asp Val Asp AsnAsp Cys Gly Asp His Ser 3650 3655 3660 Asp Glu Pro Ile Glu Glu Cys MetSer Ser Ala His Leu Cys Asp Asn 3665 3670 3675 3680 Phe Thr Glu Phe SerCys Lys Thr Asn Tyr Arg Cys Ile Pro Lys Trp 3685 3690 3695 Ala Val CysAsn Gly Val Asp Asp Cys Arg Asp Asn Ser Asp Glu Gln 3700 3705 3710 GlyCys Glu Glu Arg Thr Cys His Pro Val Gly Asp Phe Arg Cys Lys 3715 37203725 Asn His His Cys Ile Pro Leu Arg Trp Gln Cys Asp Gly Gln Asn Asp3730 3735 3740 Cys Gly Asp Asn Ser Asp Glu Glu Asn Cys Ala Pro Arg GluCys Thr 3745 3750 3755 3760 Glu Ser Glu Phe Arg Cys Val Asn Gln Gln CysIle Pro Ser Arg Trp 3765 3770 3775 Ile Cys Asp His Tyr Asn Asp Cys GlyAsp Asn Ser Asp Glu Arg Asp 3780 3785 3790 Cys Glu Met Arg Thr Cys HisPro Glu Tyr Phe Gln Cys Thr Ser Gly 3795 3800 3805 His Cys Val His SerGlu Leu Lys Cys Asp Gly Ser Ala Asp Cys Leu 3810 3815 3820 Asp Ala SerAsp Glu Ala Asp Cys Pro Thr Arg Phe Pro Asp Gly Ala 3825 3830 3835 3840Tyr Cys Gln Ala Thr Met Phe Glu Cys Lys Asn His Val Cys Ile Pro 38453850 3855 Pro Tyr Trp Lys Cys Asp Gly Asp Asp Asp Cys Gly Asp Gly SerAsp 3860 3865 3870 Glu Glu Leu His Leu Cys Leu Asp Val Pro Cys Asn SerPro Asn Arg 3875 3880 3885 Phe Arg Cys Asp Asn Asn Arg Cys Ile Tyr SerHis Glu Val Cys Asn 3890 3895 3900 Gly Val Asp Asp Cys Gly Asp Gly ThrAsp Glu Thr Glu Glu His Cys 3905 3910 3915 3920 Arg Lys Pro Thr Pro LysPro Cys Thr Glu Tyr Glu Tyr Lys Cys Gly 3925 3930 3935 Asn Gly His CysIle Pro His Asp Asn Val Cys Asp Asp Ala Asp Asp 3940 3945 3950 Cys GlyAsp Trp Ser Asp Glu Leu Gly Cys Asn Lys Gly Lys Glu Arg 3955 3960 3965Thr Cys Ala Glu Asn Ile Cys Glu Gln Asn Cys Thr Gln Leu Asn Glu 39703975 3980 Gly Gly Phe Ile Cys Ser Cys Thr Ala Gly Phe Glu Thr Asn ValPhe 3985 3990 3995 4000 Asp Arg Thr Ser Cys Leu Asp Ile Asn Glu Cys GluGln Phe Gly Thr 4005 4010 4015 Cys Pro Gln His Cys Arg Asn Thr Lys GlySer Tyr Glu Cys Val Cys 4020 4025 4030 Ala Asp Gly Phe Thr Ser Met SerAsp Arg Pro Gly Lys Arg Cys Ala 4035 4040 4045 Ala Glu Gly Ser Ser ProLeu Leu Leu Leu Pro Asp Asn Val Arg Ile 4050 4055 4060 Arg Lys Tyr AsnLeu Ser Ser Glu Arg Phe Ser Glu Tyr Leu Gln Asp 4065 4070 4075 4080 GluGlu Tyr Ile Gln Ala Val Asp Tyr Asp Trp Asp Pro Glu Asp Ile 4085 40904095 Gly Leu Ser Val Val Tyr Tyr Thr Val Arg Gly Glu Gly Ser Arg Phe4100 4105 4110 Gly Ala Ile Lys Arg Ala Tyr Ile Pro Asn Phe Glu Ser GlyArg Asn 4115 4120 4125 Asn Leu Val Gln Glu Val Asp Leu Lys Leu Lys TyrVal Met Gln Pro 4130 4135 4140 Asp Gly Ile Ala Val Asp Trp Val Gly ArgHis Ile Tyr Trp Ser Asp 4145 4150 4155 4160 Val Lys Asn Lys Arg Ile GluVal Ala Lys Leu Asp Gly Arg Tyr Arg 4165 4170 4175 Lys Trp Leu Ile SerThr Asp Leu Asp Gln Pro Ala Ala Ile Ala Val 4180 4185 4190 Asn Pro LysLeu Gly Leu Met Phe Trp Thr Asp Trp Gly Lys Glu Pro 4195 4200 4205 LysXaa Glu Ser Ala Trp Met Asn Gly Glu Asp Arg Asn Ile Leu Val 4210 42154220 Phe Glu Asp Leu Gly Trp Pro Thr Gly Leu Ser Ile Asp Tyr Leu Asn4225 4230 4235 4240 Asn Asp Arg Ile Tyr Trp Ser Asp Phe Lys Glu Asp ValIle Glu Thr 4245 4250 4255 Ile Lys Tyr Asp Gly Thr Asp Arg Arg Val IleAla Lys Glu Ala Met 4260 4265 4270 Asn Pro Tyr Ser Leu Asp Ile Phe GluAsp Gln Leu Tyr Trp Ile Ser 4275 4280 4285 Lys Glu Lys Gly Glu Val TrpLys Gln Asn Lys Phe Gly Gln Gly Lys 4290 4295 4300 Lys Glu Lys Thr LeuVal Val Asn Pro Trp Leu Thr Gln Val Arg Ile 4305 4310 4315 4320 Phe HisGln Leu Arg Tyr Asn Lys Ser Val Pro Asn Leu Cys Lys Gln 4325 4330 4335Ile Cys Ser His Leu Cys Leu Leu Arg Pro Gly Gly Tyr Ser Cys Ala 43404345 4350 Cys Pro Gln Gly Ser Ser Phe Ile Glu Gly Ser Thr Thr Glu CysAsp 4355 4360 4365 Ala Ala Ile Glu Leu Pro Ile Asn Leu Pro Pro Pro CysArg Cys Met 4370 4375 4380 His Gly Gly Asn Cys Tyr Phe Asp Glu Thr AspLeu Pro Lys Cys Lys 4385 4390 4395 4400 Cys Pro Ser Gly Tyr Thr Gly LysTyr Cys Glu Met Ala Phe Ser Lys 4405 4410 4415 Gly Ile Ser Pro Gly ThrThr Ala Val Ala Val Leu Leu Thr Ile Leu 4420 4425 4430 Leu Ile Val ValIle Gly Ala Leu Ala Ile Ala Gly Phe Phe His Tyr 4435 4440 4445 Arg ArgThr Gly Ser Leu Leu Pro Ala Leu Pro Lys Leu Pro Ser Leu 4450 4455 4460Ser Ser Leu Val Lys Pro Ser Glu Asn Gly Asn Gly Val Thr Phe Arg 44654470 4475 4480 Ser Gly Ala Asp Leu Asn Met Asp Ile Gly Val Ser Gly PheGly Pro 4485 4490 4495 Glu Thr Ala Ile Asp Arg Ser Met Ala Met Ser GluAsp Phe Val Met 4500 4505 4510 Glu Met Gly Lys Gln Pro Ile Ile Phe GluAsn Pro Met Tyr Ser Ala 4515 4520 4525 Arg Asp Ser Ala Val Lys Val ValGln Pro Ile Gln Val Thr Val Ser 4530 4535 4540 Glu Asn Val Asp Asn LysAsn Tyr Gly Ser Pro Ile Asn Pro Ser Glu 4545 4550 4555 4560 Ile Val ProGlu Thr Asn Pro Thr Ser Pro Ala Ala Asp Gly Thr Gln 4565 4570 4575 ValThr Lys Trp Asn Leu Phe Lys Arg Lys Ser Lys Gln Thr Thr Asn 4580 45854590 Phe Glu Asn Pro Ile Tyr Ala Gln Met Glu Asn Glu Gln Lys Glu Ser4595 4600 4605 Val Ala Ala Thr Pro Pro Pro Ser Pro Ser Leu Pro Ala LysPro Lys 4610 4615 4620 Pro Pro Ser Arg Arg Asp Pro Thr Pro Thr Tyr SerAla Thr Glu Asp 4625 4630 4635 4640 Thr Phe Lys Asp Thr Ala Asn Leu ValLys Glu Asp Ser Glu Val 4645 4650 4655 14044 base pairs nucleic acidsingle linear cDNA NO NO Homo sapiens Parathyroid CDS 65..14032 89TGCGGTGTGC TACGCGCGCC CACCTCCCGG GGAAGGAACG GCGAGGCCGG GGACCGTCGC 60GGAG ATG GAT CGC GGG CCG GCA GCA GTG GCG TGC ACG CTG CTC CTG GCT 109 MetAsp Arg Gly Pro Ala Ala Val Ala Cys Thr Leu Leu Leu Ala 4660 4665 4670CTC GTC GCC TGC CTA GCC CCG GCC AGT GGC CAA GAA TGT GAC AGT GCG 157 LeuVal Ala Cys Leu Ala Pro Ala Ser Gly Gln Glu Cys Asp Ser Ala 4675 46804685 CAT TTT CGC TGT GGA AGT GGG CAT TGC ATC CCT GCA GAC TGG AGG TGT 205His Phe Arg Cys Gly Ser Gly His Cys Ile Pro Ala Asp Trp Arg Cys 46904695 4700 GAT GGG ACC AAA GAC TGT TCA GAT GAC GCG GAT GAA ATT GGC TGCGCT 253 Asp Gly Thr Lys Asp Cys Ser Asp Asp Ala Asp Glu Ile Gly Cys Ala4705 4710 4715 GTT GTG ACC TGC CAG CAG GGC TAT TTC AAG TGC CAG AGT GAGGGA CAA 301 Val Val Thr Cys Gln Gln Gly Tyr Phe Lys Cys Gln Ser Glu GlyGln 4720 4725 4730 4735 TGC ATC CCC AGC TCC TGG GTG TGT GAC CAA GAT CAAGAC TGT GAT GAT 349 Cys Ile Pro Ser Ser Trp Val Cys Asp Gln Asp Gln AspCys Asp Asp 4740 4745 4750 GGC TCA GAT GAA CGT CAA GAT TGC TCA CAA AGTACA TGC TCA AGT CAT 397 Gly Ser Asp Glu Arg Gln Asp Cys Ser Gln Ser ThrCys Ser Ser His 4755 4760 4765 CAG ATA ACA TGC TCC AAT GGT CAG TGT ATCCCA AGT GAA TAC AGG TGC 445 Gln Ile Thr Cys Ser Asn Gly Gln Cys Ile ProSer Glu Tyr Arg Cys 4770 4775 4780 GAC CAC GTC AGA GAC TGC CCC GAT GGAGCT GAT GAG AAT GAC TGC CAG 493 Asp His Val Arg Asp Cys Pro Asp Gly AlaAsp Glu Asn Asp Cys Gln 4785 4790 4795 TAC CCA ACA TGT GAG CAG CTT ACTTGT GAC AAT GGG GCC TGC TAT AAC 541 Tyr Pro Thr Cys Glu Gln Leu Thr CysAsp Asn Gly Ala Cys Tyr Asn 4800 4805 4810 4815 ACC AGT CAG AAG TGT GATTGG AAA GTT GAT TGC AGG GAC TCC TCA GAT 589 Thr Ser Gln Lys Cys Asp TrpLys Val Asp Cys Arg Asp Ser Ser Asp 4820 4825 4830 GAA ATC AAC TGC ACTGAG ATA TGC TTG CAC AAT GAG TTT TCA TGT GGC 637 Glu Ile Asn Cys Thr GluIle Cys Leu His Asn Glu Phe Ser Cys Gly 4835 4840 4845 AAT GGA GAG TGTATC CCT CGT GCT TAT GTC TGT GAC CAT GAC AAT GAT 685 Asn Gly Glu Cys IlePro Arg Ala Tyr Val Cys Asp His Asp Asn Asp 4850 4855 4860 TGC CAA GACGGC AGT GAC GAA CAT GCT TGC AAC TAT CCG ACC TGC GGT 733 Cys Gln Asp GlySer Asp Glu His Ala Cys Asn Tyr Pro Thr Cys Gly 4865 4870 4875 GGT TACCAG TTC ACT TGC CCC AGT GGC CGA TGC ATT TAT CAA AAC TGG 781 Gly Tyr GlnPhe Thr Cys Pro Ser Gly Arg Cys Ile Tyr Gln Asn Trp 4880 4885 4890 4895GTT TGT GAT GGA GAA GAT GAC TGT AAA GAT AAT GGA GAT GAA GAT GGA 829 ValCys Asp Gly Glu Asp Asp Cys Lys Asp Asn Gly Asp Glu Asp Gly 4900 49054910 TGT GAA AGC GGT CCT CAT GAT GTT CAT AAA TGT TCC CCA AGA GAA TGG 877Cys Glu Ser Gly Pro His Asp Val His Lys Cys Ser Pro Arg Glu Trp 49154920 4925 TCT TGC CCA GAG TCG GGA CGA TGC ATC TCC ATT TAT AAA GTT TGTGAT 925 Ser Cys Pro Glu Ser Gly Arg Cys Ile Ser Ile Tyr Lys Val Cys Asp4930 4935 4940 GGG ATT TTA GAT TGC CCA GGA AGA GAA GAT GAA AAC AAC ACTAGT ACC 973 Gly Ile Leu Asp Cys Pro Gly Arg Glu Asp Glu Asn Asn Thr SerThr 4945 4950 4955 GGA AAA TAC TGT AGT ATG ACT CTG TGC TCT GCC TTG AACTGC CAG TAC 1021 Gly Lys Tyr Cys Ser Met Thr Leu Cys Ser Ala Leu Asn CysGln Tyr 4960 4965 4970 4975 CAG TGC CAT GAG ACG CCG TAT GGA GGA GCG TGTTTT TGT CCC CCA GGT 1069 Gln Cys His Glu Thr Pro Tyr Gly Gly Ala Cys PheCys Pro Pro Gly 4980 4985 4990 TAT ATC ATC AAC CAC AAT GAC AGC CGT ACCTGT GTT GAG TTT GAT GAT 1117 Tyr Ile Ile Asn His Asn Asp Ser Arg Thr CysVal Glu Phe Asp Asp 4995 5000 5005 TGC CAG ATA TGG GGA ATT TGT GAC CAGAAG TGT GAA AGC CGA CCT GGC 1165 Cys Gln Ile Trp Gly Ile Cys Asp Gln LysCys Glu Ser Arg Pro Gly 5010 5015 5020 CGT CAC CTG TGC CAC TGT GAA GAAGGG TAT ATC TTG GAG CGT GGA CAG 1213 Arg His Leu Cys His Cys Glu Glu GlyTyr Ile Leu Glu Arg Gly Gln 5025 5030 5035 TAT TGC AAA GCT AAT GAT TCCTTT GGC GAG GCC TCC ATT ATC TTC TCC 1261 Tyr Cys Lys Ala Asn Asp Ser PheGly Glu Ala Ser Ile Ile Phe Ser 5040 5045 5050 5055 AAT GGT CGG GAT TTGTTA ATT GGT GAT ATT CAT GGA AGG AGC TTC CGG 1309 Asn Gly Arg Asp Leu LeuIle Gly Asp Ile His Gly Arg Ser Phe Arg 5060 5065 5070 ATC CTA GTG GAGTCT CAG AAT CGT GGA GTG GCC GTG GGT GTG GCT TTC 1357 Ile Leu Val Glu SerGln Asn Arg Gly Val Ala Val Gly Val Ala Phe 5075 5080 5085 CAC TAT CACCTG CAA AGA GTT TTT TGG ACA GAC ACC GTG CAA AAT AAG 1405 His Tyr His LeuGln Arg Val Phe Trp Thr Asp Thr Val Gln Asn Lys 5090 5095 5100 GTT TTTTCA GTT GAC ATT AAT GGT TTA AAT ATC CAA GAG GTT CTC AAT 1453 Val Phe SerVal Asp Ile Asn Gly Leu Asn Ile Gln Glu Val Leu Asn 5105 5110 5115 GTTTCT GTT GAA ACC CCA GAG AAC CTG GCT GTG GAC TGG GTT AAT AAT 1501 Val SerVal Glu Thr Pro Glu Asn Leu Ala Val Asp Trp Val Asn Asn 5120 5125 51305135 AAA ATC TAT CTA GTG GAA ACC AAG GTC AAC CGC ATA GAT ATG GTA AAT1549 Lys Ile Tyr Leu Val Glu Thr Lys Val Asn Arg Ile Asp Met Val Asn5140 5145 5150 TTG GAT GGA AGC TAT CGG GTT ACC CTT ATA ACT GAA AAC TTGGGG CAT 1597 Leu Asp Gly Ser Tyr Arg Val Thr Leu Ile Thr Glu Asn Leu GlyHis 5155 5160 5165 CCT AGA GGA ATT GCC GTG GAC CCA ACT GTT GGT TAT TTATTT TTC TCA 1645 Pro Arg Gly Ile Ala Val Asp Pro Thr Val Gly Tyr Leu PhePhe Ser 5170 5175 5180 GAT TGG GAG AGC CTT TCT GGG GAA CCT AAG CTG GAAAGG GCA TTC ATG 1693 Asp Trp Glu Ser Leu Ser Gly Glu Pro Lys Leu Glu ArgAla Phe Met 5185 5190 5195 GAT GGC AGC AAC CGT AAA GAC TTG GTG AAA ACAAAG CTG GGA TGG CCT 1741 Asp Gly Ser Asn Arg Lys Asp Leu Val Lys Thr LysLeu Gly Trp Pro 5200 5205 5210 5215 GCT GGG GTA ACT CTG GAT ATG ATA TCGAAG CGT GTT TAC TGG GTT GAC 1789 Ala Gly Val Thr Leu Asp Met Ile Ser LysArg Val Tyr Trp Val Asp 5220 5225 5230 TCT CGG TTT GAT TAC ATT GAA ACTGTA ACT TAT GAT GGA ATT CAA AGG 1837 Ser Arg Phe Asp Tyr Ile Glu Thr ValThr Tyr Asp Gly Ile Gln Arg 5235 5240 5245 AAG ACT GTA GTT CAT GGA GGCTCC CTC ATT CCT CAT CCC TTT GGA GTA 1885 Lys Thr Val Val His Gly Gly SerLeu Ile Pro His Pro Phe Gly Val 5250 5255 5260 AGC TTA TTT GAA GGT CAGGTG TTC TTT ACA GAT TGG ACA AAG ATG GCC 1933 Ser Leu Phe Glu Gly Gln ValPhe Phe Thr Asp Trp Thr Lys Met Ala 5265 5270 5275 GTG CTG AAG GCA AACAAG TTC ACA GAG ACC AAC CCA CAA GTG TAC TAC 1981 Val Leu Lys Ala Asn LysPhe Thr Glu Thr Asn Pro Gln Val Tyr Tyr 5280 5285 5290 5295 CAG GCT TCCCTG AGG CCC TAT GGA GTG ACT GTT TAC CAT TCC CTC AGA 2029 Gln Ala Ser LeuArg Pro Tyr Gly Val Thr Val Tyr His Ser Leu Arg 5300 5305 5310 CAG CCCTAT GCT ACC AAT CCG TGT AAA GAT AAC AAT GGG GGC TGT GAG 2077 Gln Pro TyrAla Thr Asn Pro Cys Lys Asp Asn Asn Gly Gly Cys Glu 5315 5320 5325 CAGGTC TGT GTY CTC AGC CAC AGA ACA GAT AAT GAT GGT TTG GGT TTC 2125 Gln ValCys Val Leu Ser His Arg Thr Asp Asn Asp Gly Leu Gly Phe 5330 5335 5340CGT TGC AAG TGC ACA TTC GGC TTC CAA CTG GAT ACA GAT GAG CGC CAC 2173 ArgCys Lys Cys Thr Phe Gly Phe Gln Leu Asp Thr Asp Glu Arg His 5345 53505355 TGC ATT GCT GTT CAG AAT TTC CTC ATT TTT TCA TCC CAA GTT GCT ATT2221 Cys Ile Ala Val Gln Asn Phe Leu Ile Phe Ser Ser Gln Val Ala Ile5360 5365 5370 5375 CGT GGG ATC CCG TTC ACC TTG TCT ACC CAG GAA GAT GTCATG GTT CCA 2269 Arg Gly Ile Pro Phe Thr Leu Ser Thr Gln Glu Asp Val MetVal Pro 5380 5385 5390 GTT TCG GGG AAT CCT TCT TTC TTT GTC GGG ATT GATTTT GAC GCC CAG 2317 Val Ser Gly Asn Pro Ser Phe Phe Val Gly Ile Asp PheAsp Ala Gln 5395 5400 5405 GAC AGC ACT ATC TTT TTT TCA GAT ATG TCA AAACAC ATG ATT TTT AAG 2365 Asp Ser Thr Ile Phe Phe Ser Asp Met Ser Lys HisMet Ile Phe Lys 5410 5415 5420 CAA AAG ATT GAT GGC ACA GGA AGA GAA ATTCTC GCA GCT AAC AGG GTG 2413 Gln Lys Ile Asp Gly Thr Gly Arg Glu Ile LeuAla Ala Asn Arg Val 5425 5430 5435 GAA AAT GTT GAA AGT TTG GCT TTT GATTGG ATT TCA AAG AAT CTC TAT 2461 Glu Asn Val Glu Ser Leu Ala Phe Asp TrpIle Ser Lys Asn Leu Tyr 5440 5445 5450 5455 TGG ACA GAC TCT CAT TAC AAGAGT ATC AGT GTC ATG AGG CTA GCT GAT 2509 Trp Thr Asp Ser His Tyr Lys SerIle Ser Val Met Arg Leu Ala Asp 5460 5465 5470 AAA ACG AGA CGC ACG GTAGTT CAG TAT TTA AAT AAC CCA CGG TCG GTG 2557 Lys Thr Arg Arg Thr Val ValGln Tyr Leu Asn Asn Pro Arg Ser Val 5475 5480 5485 GTA GTT CAT CCT TTTGCC GGG TAT CTA TTC TTC ACT GAT TGG TTC CGT 2605 Val Val His Pro Phe AlaGly Tyr Leu Phe Phe Thr Asp Trp Phe Arg 5490 5495 5500 CCT GCT AAA ATTATG AGA GCA TGG AGT GAC GGA TCT CAC CTC TTG CCT 2653 Pro Ala Lys Ile MetArg Ala Trp Ser Asp Gly Ser His Leu Leu Pro 5505 5510 5515 GTA ATA AACACT ACT CTT GGA TGG CCC AAT GGC TTG GCC ATC GAT TGG 2701 Val Ile Asn ThrThr Leu Gly Trp Pro Asn Gly Leu Ala Ile Asp Trp 5520 5525 5530 5535 GCTGCT TCA CGA TTG TAC TGG GTA GAT GCC TAT TTT GAT AAA ATT GAG 2749 Ala AlaSer Arg Leu Tyr Trp Val Asp Ala Tyr Phe Asp Lys Ile Glu 5540 5545 5550CAC AGC ACC TTT GAT GGT TTA GAC AGA AGA AGA CTG GGC CAT ATA GAG 2797 HisSer Thr Phe Asp Gly Leu Asp Arg Arg Arg Leu Gly His Ile Glu 5555 55605565 CAG ATG ACA CAT CCG TTT GGA CTT GCC ATC TTT GGA GAG CAT TTA TTT2845 Gln Met Thr His Pro Phe Gly Leu Ala Ile Phe Gly Glu His Leu Phe5570 5575 5580 TTT ACT GAC TGG AGA CTG GGT GCC ATT ATT CGA GTC AGG AAAGCA GAT 2893 Phe Thr Asp Trp Arg Leu Gly Ala Ile Ile Arg Val Arg Lys AlaAsp 5585 5590 5595 GGT GGA GAA ATG ACA GTT ATC CGA AGT GGC ATT GCT TACATA CTG CAT 2941 Gly Gly Glu Met Thr Val Ile Arg Ser Gly Ile Ala Tyr IleLeu His 5600 5605 5610 5615 TTG AAA TCG TAT GAT GTC AAC ATC CAG ACT GGTTCT AAC GCC TGT AAT 2989 Leu Lys Ser Tyr Asp Val Asn Ile Gln Thr Gly SerAsn Ala Cys Asn 5620 5625 5630 CAA CCC ACG CAT CCT AAC GGT GAC TGC AGCCAC TTC TGC TTC CCG GTG 3037 Gln Pro Thr His Pro Asn Gly Asp Cys Ser HisPhe Cys Phe Pro Val 5635 5640 5645 CCA AAT TTC CAG CGA GTG TGT GGG TGCCCT TAT GGA ATG AGG CTG GCT 3085 Pro Asn Phe Gln Arg Val Cys Gly Cys ProTyr Gly Met Arg Leu Ala 5650 5655 5660 TCC AAT CAC TTG ACA TGC GAG GGGGAC CCA ACM AAT GAA CCA CCC ACG 3133 Ser Asn His Leu Thr Cys Glu Gly AspPro Thr Asn Glu Pro Pro Thr 5665 5670 5675 GAG CAG TGT GGC TTA TTT TCCTTC CCC TGT AAA AAT GGC AGA TGT GTG 3181 Glu Gln Cys Gly Leu Phe Ser PhePro Cys Lys Asn Gly Arg Cys Val 5680 5685 5690 5695 CCC AAT TAC TAT CTCTGT GAT GGA GTC GAT GAT TGT CAT GAT AAC AGT 3229 Pro Asn Tyr Tyr Leu CysAsp Gly Val Asp Asp Cys His Asp Asn Ser 5700 5705 5710 GAT GAG CAA CTATGT GGC ACA CTT AAT AAT ACC TGT TCA TCT TCG GCG 3277 Asp Glu Gln Leu CysGly Thr Leu Asn Asn Thr Cys Ser Ser Ser Ala 5715 5720 5725 TTC ACC TGTGGC CAT GGG GAG TGC ATT CCT GCA CAC TGG CGC TGT GAC 3325 Phe Thr Cys GlyHis Gly Glu Cys Ile Pro Ala His Trp Arg Cys Asp 5730 5735 5740 AAA CGCAAC GAC TGT GTG GAT GGC AGT GAT GAG CAC AAC TGC CCC ACC 3373 Lys Arg AsnAsp Cys Val Asp Gly Ser Asp Glu His Asn Cys Pro Thr 5745 5750 5755 CACGCA CCT GCT TCC TGC CTT GAC ACC CAA TAC ACC TGT GAT AAT CAC 3421 His AlaPro Ala Ser Cys Leu Asp Thr Gln Tyr Thr Cys Asp Asn His 5760 5765 57705775 CAG TGT ATC TCA AAG AAC TGG GTC TGT GAC ACA GAC AAT GAT TGT GGG3469 Gln Cys Ile Ser Lys Asn Trp Val Cys Asp Thr Asp Asn Asp Cys Gly5780 5785 5790 GAT GGA TCT GAT GAA AAG AAC TGC AAT TCG ACA GAG ACA TGCCAA CCT 3517 Asp Gly Ser Asp Glu Lys Asn Cys Asn Ser Thr Glu Thr Cys GlnPro 5795 5800 5805 AGT CAG TTT AAT TGC CCC AAT CAT CGA TGT ATT GAC CTATCG TTT GTC 3565 Ser Gln Phe Asn Cys Pro Asn His Arg Cys Ile Asp Leu SerPhe Val 5810 5815 5820 TGT GAT GGT GAC AAG GAT TGT GTT GAT GGA TCT GATGAG GTT GGT TGT 3613 Cys Asp Gly Asp Lys Asp Cys Val Asp Gly Ser Asp GluVal Gly Cys 5825 5830 5835 GTA TTA AAC TGT ACT GCT TCT CAA TTC AAG TGTGCC AGT GGG GAT AAA 3661 Val Leu Asn Cys Thr Ala Ser Gln Phe Lys Cys AlaSer Gly Asp Lys 5840 5845 5850 5855 TGT ATT GGC GTC ACA AAT CGT TGT GATGGT GTT TTT GAT TGC AGT GAC 3709 Cys Ile Gly Val Thr Asn Arg Cys Asp GlyVal Phe Asp Cys Ser Asp 5860 5865 5870 AAC TCG GAT GAA GCG GGC TGT CCAACC AGG CCT CCT GGT ATG TGC CAC 3757 Asn Ser Asp Glu Ala Gly Cys Pro ThrArg Pro Pro Gly Met Cys His 5875 5880 5885 TCA GAT GAA TTT CAG TGC CAAGAA GAT GGT ATC TGC ATC CCG AAC TTC 3805 Ser Asp Glu Phe Gln Cys Gln GluAsp Gly Ile Cys Ile Pro Asn Phe 5890 5895 5900 TGG GAA TGT GAT GGG CATCCA GAC TGC CTC TAT GGA TCT GAT GAG CAC 3853 Trp Glu Cys Asp Gly His ProAsp Cys Leu Tyr Gly Ser Asp Glu His 5905 5910 5915 AAT GCC TGT GTC CCCAAG ACT TGC CCT TCA TCA TAT TTC CAC TGT GAC 3901 Asn Ala Cys Val Pro LysThr Cys Pro Ser Ser Tyr Phe His Cys Asp 5920 5925 5930 5935 AAC GGA AACTGC ATC CAC AGG GCA TGG CTC TGT GAT CGG GAC AAT GAC 3949 Asn Gly Asn CysIle His Arg Ala Trp Leu Cys Asp Arg Asp Asn Asp 5940 5945 5950 TGC GGGGAT ATG AGT GAT GAG AAG GAC TGC CCT ACT CAG CCC TTT CGC 3997 Cys Gly AspMet Ser Asp Glu Lys Asp Cys Pro Thr Gln Pro Phe Arg 5955 5960 5965 TGTCCT AGT TGG CAA TGG CAG TGT CTT GGC CAT AAC ATC TGT GTG AAT 4045 Cys ProSer Trp Gln Trp Gln Cys Leu Gly His Asn Ile Cys Val Asn 5970 5975 5980CTG AGT GTA GTG TGT GAT GGC ATC TTT GAC TGC CCC AAT GGG ACA GAT 4093 LeuSer Val Val Cys Asp Gly Ile Phe Asp Cys Pro Asn Gly Thr Asp 5985 59905995 GAG TCC CCA CTT TGC AAT GGG AAC AGC TGC TCA GAT TTC AAT GGT GGT4141 Glu Ser Pro Leu Cys Asn Gly Asn Ser Cys Ser Asp Phe Asn Gly Gly6000 6005 6010 6015 TGT ACT CAC GAG TGT GTT CAA GAG CCC TTT GGG GCT AAATGC CTA TGT 4189 Cys Thr His Glu Cys Val Gln Glu Pro Phe Gly Ala Lys CysLeu Cys 6020 6025 6030 CCA TTG GGA TTC TTA CTT GCC AAT GAT TCT AAG ACCTGT GAA GAC ATA 4237 Pro Leu Gly Phe Leu Leu Ala Asn Asp Ser Lys Thr CysGlu Asp Ile 6035 6040 6045 GAT GAA TGT GAT ATT CTA GGC TCT TGT AGC CAGCAC TGT TAC AAT ATG 4285 Asp Glu Cys Asp Ile Leu Gly Ser Cys Ser Gln HisCys Tyr Asn Met 6050 6055 6060 AGA GGT TCT TTC CGG TGC TCG TGT GAT ACAGGC TAC ATG TTA GAA AGT 4333 Arg Gly Ser Phe Arg Cys Ser Cys Asp Thr GlyTyr Met Leu Glu Ser 6065 6070 6075 GAT GGG AGG ACT TGC AAA GTT ACA GCATCT GAG AGT CTG CTG TTA CTT 4381 Asp Gly Arg Thr Cys Lys Val Thr Ala SerGlu Ser Leu Leu Leu Leu 6080 6085 6090 6095 GTG GCA AGT CAG AAC AAA ATTATT GCC GAC AGT GTC ACC TCC CAG GTC 4429 Val Ala Ser Gln Asn Lys Ile IleAla Asp Ser Val Thr Ser Gln Val 6100 6105 6110 CAC AAT ATC TAT TCA TTGGTC GAG AAT GGT TCT TAC ATT GTA GCT GTT 4477 His Asn Ile Tyr Ser Leu ValGlu Asn Gly Ser Tyr Ile Val Ala Val 6115 6120 6125 GAT TTT GAT TCA ATTAGT GGT CGT ATC TTT TGG TCT GAT GCA ACT CAG 4525 Asp Phe Asp Ser Ile SerGly Arg Ile Phe Trp Ser Asp Ala Thr Gln 6130 6135 6140 GGT AAA ACC TGGAGT GCG TTT CAA AAT GGA ACG GAC AGA AGA GTG GTA 4573 Gly Lys Thr Trp SerAla Phe Gln Asn Gly Thr Asp Arg Arg Val Val 6145 6150 6155 TTT GAC AGTAGC ATC ATC TTG ACT GAA ACT ATT GCA ATA GAT TGG GTA 4621 Phe Asp Ser SerIle Ile Leu Thr Glu Thr Ile Ala Ile Asp Trp Val 6160 6165 6170 6175 GGTCGT AAT CTT TAC TGG ACA GAC TAT GCT CTG GAA ACA ATT GAA GTC 4669 Gly ArgAsn Leu Tyr Trp Thr Asp Tyr Ala Leu Glu Thr Ile Glu Val 6180 6185 6190TCC AAA ATT GAT GGG AGC CAC AGG ACT GTG CTG ATT AGT AAA AAC CTA 4717 SerLys Ile Asp Gly Ser His Arg Thr Val Leu Ile Ser Lys Asn Leu 6195 62006205 ACA AAT CCA AGA GGA CTA GCA TTA GAT CCC AGA ATG AAT GAG CAT CTA4765 Thr Asn Pro Arg Gly Leu Ala Leu Asp Pro Arg Met Asn Glu His Leu6210 6215 6220 CTG TTC TGG TCT GAC TGG GGC CAC CAC CCT CGC ATC GAG CGAGCC AGC 4813 Leu Phe Trp Ser Asp Trp Gly His His Pro Arg Ile Glu Arg AlaSer 6225 6230 6235 ATG GAC GGC AGC ATG CGC ACT GTC ATT GTC CAG GAC AAGATC TTC TGG 4861 Met Asp Gly Ser Met Arg Thr Val Ile Val Gln Asp Lys IlePhe Trp 6240 6245 6250 6255 CCC TGC GGC TTA ACT ATT GAC TAC CCC AAC AGACTG CTC TAC TTC ATG 4909 Pro Cys Gly Leu Thr Ile Asp Tyr Pro Asn Arg LeuLeu Tyr Phe Met 6260 6265 6270 GAC TCC TAT CTT GAT TAC ATG GAC TTT TGTGAT TAT AAT GGA CAC CAT 4957 Asp Ser Tyr Leu Asp Tyr Met Asp Phe Cys AspTyr Asn Gly His His 6275 6280 6285 CGG AGA CAG GTG ATA GCC AGT GAT TTGATT ATA CGG CAC CCC TAT GCC 5005 Arg Arg Gln Val Ile Ala Ser Asp Leu IleIle Arg His Pro Tyr Ala 6290 6295 6300 CTA ACT CTC TTT GAA GAC TCT GTGTAC TGG ACT GAC CGT GCT ACT CGT 5053 Leu Thr Leu Phe Glu Asp Ser Val TyrTrp Thr Asp Arg Ala Thr Arg 6305 6310 6315 CGG GTT ATG CGA GCC AAC AAGTGG CAT GGA GGG AAC CAG TCA GTT GTA 5101 Arg Val Met Arg Ala Asn Lys TrpHis Gly Gly Asn Gln Ser Val Val 6320 6325 6330 6335 ATG TAT AAT ATT CAATGG CCC CTT GGG ATT GTT GCG GTT CAT CCT TCG 5149 Met Tyr Asn Ile Gln TrpPro Leu Gly Ile Val Ala Val His Pro Ser 6340 6345 6350 AAA CAA CCA AATTCC GTG AAT CCA TGT GCC TTT TCC CGC TGC AGC CAT 5197 Lys Gln Pro Asn SerVal Asn Pro Cys Ala Phe Ser Arg Cys Ser His 6355 6360 6365 CTC TGC CTGCTT TCC TCA CAG GGG CCT CAT TTT TAC TCC TGT GTT TGT 5245 Leu Cys Leu LeuSer Ser Gln Gly Pro His Phe Tyr Ser Cys Val Cys 6370 6375 6380 CCT TCAGGA TGG AGT CTG TCT CCT GAT CTC CTG AAT TGC TTG AGA GAT 5293 Pro Ser GlyTrp Ser Leu Ser Pro Asp Leu Leu Asn Cys Leu Arg Asp 6385 6390 6395 GATCAA CCT TTC TTA ATA ACT GTA AGG CAA CAT ATA ATT TTT GGA ATC 5341 Asp GlnPro Phe Leu Ile Thr Val Arg Gln His Ile Ile Phe Gly Ile 6400 6405 64106415 TCC CTT AAT CCT GAG GTG AAG AGC AAT GAT GCT ATG GTC CCC ATA GCA5389 Ser Leu Asn Pro Glu Val Lys Ser Asn Asp Ala Met Val Pro Ile Ala6420 6425 6430 GGG ATA CAG AAT GGT TTA GAT GTT GAA TTT GAT GAT GCT GAGCAA TAC 5437 Gly Ile Gln Asn Gly Leu Asp Val Glu Phe Asp Asp Ala Glu GlnTyr 6435 6440 6445 ATC TAT TGG GTT GAA AAT CCA GGT GAA ATT CAC AGA GTGAAG ACA GAT 5485 Ile Tyr Trp Val Glu Asn Pro Gly Glu Ile His Arg Val LysThr Asp 6450 6455 6460 GGC ACC AAC AGG ACA GTA TTT GCT TCT ATA TCT ATGGTG GGG CCT TCT 5533 Gly Thr Asn Arg Thr Val Phe Ala Ser Ile Ser Met ValGly Pro Ser 6465 6470 6475 ATG AAC CTG GCC TTA GAT TGG ATT TCA AGA AACCTT TAT TCT ACC AAT 5581 Met Asn Leu Ala Leu Asp Trp Ile Ser Arg Asn LeuTyr Ser Thr Asn 6480 6485 6490 6495 CCT AGA ACT CAG TCA ATC GAG GTT TTGACA CTC CAC GGA GAT ATC AGA 5629 Pro Arg Thr Gln Ser Ile Glu Val Leu ThrLeu His Gly Asp Ile Arg 6500 6505 6510 TAC AGA AAA ACA TTG ATT GCC AATGAT GGG ACA GCT CTT GGA GTT GGC 5677 Tyr Arg Lys Thr Leu Ile Ala Asn AspGly Thr Ala Leu Gly Val Gly 6515 6520 6525 TTT CCA ATT GGC ATA ACT GTTGAT CCT GCT CGT GGG AAG CTG TAC TGG 5725 Phe Pro Ile Gly Ile Thr Val AspPro Ala Arg Gly Lys Leu Tyr Trp 6530 6535 6540 TCA GAC CAA GGA ACT GACAGT GGG GTT CCT GCC AAG ATC GCC AGT GCT 5773 Ser Asp Gln Gly Thr Asp SerGly Val Pro Ala Lys Ile Ala Ser Ala 6545 6550 6555 AAC ATG GAT GGC ACATCT GTG AAA ACT CTC TTT ACT GGG AAC CTC GAA 5821 Asn Met Asp Gly Thr SerVal Lys Thr Leu Phe Thr Gly Asn Leu Glu 6560 6565 6570 6575 CAC CTG GAGTGT GTC ACT CTT GAC ATC GAA GAG CAG AAA CTC TAC TGG 5869 His Leu Glu CysVal Thr Leu Asp Ile Glu Glu Gln Lys Leu Tyr Trp 6580 6585 6590 GCA GTCACT GGA AGA GGA GTG ATT GAA AGA GGA AAC GTG GAT GGA ACA 5917 Ala Val ThrGly Arg Gly Val Ile Glu Arg Gly Asn Val Asp Gly Thr 6595 6600 6605 GATCGA ATG ATC CTG GTA CAC CAG CTT TCC CAC CCC TGG GGA ATT GCA 5965 Asp ArgMet Ile Leu Val His Gln Leu Ser His Pro Trp Gly Ile Ala 6610 6615 6620GTC CAT GAT TCT TTC CTT TAT TAT ACT GAT GAA CAG TAT GAG GTC ATT 6013 ValHis Asp Ser Phe Leu Tyr Tyr Thr Asp Glu Gln Tyr Glu Val Ile 6625 66306635 GAA AGA GTT GAT AAG GCC ACT GGG GCC AAC AAA ATA GTC TTG AGA GAT6061 Glu Arg Val Asp Lys Ala Thr Gly Ala Asn Lys Ile Val Leu Arg Asp6640 6645 6650 6655 AAT GTT CCA AAT CTG AGG GGT CTT CAA GTT TAT CAC AGACGC AAT GCC 6109 Asn Val Pro Asn Leu Arg Gly Leu Gln Val Tyr His Arg ArgAsn Ala 6660 6665 6670 GCC GAA TCC TCA AAT GGC TGT AGC AAC AAC ATG AATGCC TGT CAG CAG 6157 Ala Glu Ser Ser Asn Gly Cys Ser Asn Asn Met Asn AlaCys Gln Gln 6675 6680 6685 ATT TGC CTG CCT GTA CCA GGA GGA TTG TTT TCCTGC GCC TGT GCC ACT 6205 Ile Cys Leu Pro Val Pro Gly Gly Leu Phe Ser CysAla Cys Ala Thr 6690 6695 6700 GGA TTT AAA CTC AAT CCT GAT AAT CGG TCCTGC TCT CCA TAT AAC TCT 6253 Gly Phe Lys Leu Asn Pro Asp Asn Arg Ser CysSer Pro Tyr Asn Ser 6705 6710 6715 TTC ATT GTT GTT TCA ATG CTG TCT GCAATC AGA GGC TTT AGC TTG GAA 6301 Phe Ile Val Val Ser Met Leu Ser Ala IleArg Gly Phe Ser Leu Glu 6720 6725 6730 6735 TTG TCA GAT CAT TCA GAA ACCATG GTG CCG GTG GCA GGC CAA GGA CGA 6349 Leu Ser Asp His Ser Glu Thr MetVal Pro Val Ala Gly Gln Gly Arg 6740 6745 6750 AAC GCA CTG CAT GTG GATGTG GAT GTG TCC TCT GGC TTT ATT TAT TGG 6397 Asn Ala Leu His Val Asp ValAsp Val Ser Ser Gly Phe Ile Tyr Trp 6755 6760 6765 TGT GAT TTT AGC AGCTCA GTG GCA TCT GAT AAT GCG ATC CGT AGA ATT 6445 Cys Asp Phe Ser Ser SerVal Ala Ser Asp Asn Ala Ile Arg Arg Ile 6770 6775 6780 AAA CCA GAT GGATCT TCT CTG ATG AAC ATT GTG ACA CAT GGA ATA GGA 6493 Lys Pro Asp Gly SerSer Leu Met Asn Ile Val Thr His Gly Ile Gly 6785 6790 6795 GAA AAT GGAGTC CGG GGT ATT GCA GTG GAT TGG GTA GCA GGA AAT CTT 6541 Glu Asn Gly ValArg Gly Ile Ala Val Asp Trp Val Ala Gly Asn Leu 6800 6805 6810 6815 TATTTC ACC AAT GCC TTT GTT TCT GAA ACA CTG ATA GAA GTT CTG CGG 6589 Tyr PheThr Asn Ala Phe Val Ser Glu Thr Leu Ile Glu Val Leu Arg 6820 6825 6830ATC AAT ACT ACT TAC CGC CGT GTT CTT CTT AAA GTC ACA GTG GAC ATG 6637 IleAsn Thr Thr Tyr Arg Arg Val Leu Leu Lys Val Thr Val Asp Met 6835 68406845 CCT AGG CAT ATT GTT GTA GAT CCC AAG AAC AGA TAC CTC TTC TGG GCT6685 Pro Arg His Ile Val Val Asp Pro Lys Asn Arg Tyr Leu Phe Trp Ala6850 6855 6860 GAC TAT GGG CAG AGA CCA AAG ATT GAG CGT TCT TTC CTT GACTGT ACC 6733 Asp Tyr Gly Gln Arg Pro Lys Ile Glu Arg Ser Phe Leu Asp CysThr 6865 6870 6875 AAT CGA ACA GTG CTT GTG TCA GAG GGC ATT GTC ACA CCACGG GGC TTG 6781 Asn Arg Thr Val Leu Val Ser Glu Gly Ile Val Thr Pro ArgGly Leu 6880 6885 6890 6895 GCA GTG GAC CGA AGT GAT GGC TAC GTT TAT TGGGTT GAT GAT TCT TTA 6829 Ala Val Asp Arg Ser Asp Gly Tyr Val Tyr Trp ValAsp Asp Ser Leu 6900 6905 6910 GAT ATA ATT GCA AGG ATT CGT ATC AAT GGAGAG AAC TCT GAA GTG ATT 6877 Asp Ile Ile Ala Arg Ile Arg Ile Asn Gly GluAsn Ser Glu Val Ile 6915 6920 6925 CGT TAT GGC AGT CGT TAC CCA ACT CCTTAT GGC ATC ACT GTT TTT GAA 6925 Arg Tyr Gly Ser Arg Tyr Pro Thr Pro TyrGly Ile Thr Val Phe Glu 6930 6935 6940 AAT TCT ATC ATA TGG GTA GAT AGGAAT TTG AAA AAG ATC TTC CAA GCC 6973 Asn Ser Ile Ile Trp Val Asp Arg AsnLeu Lys Lys Ile Phe Gln Ala 6945 6950 6955 AGC AAG GAA CCA GAG AAC ACAGAG CCA CCC ACA GTG ATA AGA GAC AAT 7021 Ser Lys Glu Pro Glu Asn Thr GluPro Pro Thr Val Ile Arg Asp Asn 6960 6965 6970 6975 ATC AAC TGG CTA AGAGAT GTG ACC ATC TTT GAC AAG CAA GTC CAG CCC 7069 Ile Asn Trp Leu Arg AspVal Thr Ile Phe Asp Lys Gln Val Gln Pro 6980 6985 6990 CGG TCA CCA GCAGAG GTC AAC AAC AAC CCT TGC TTG GAA AAC AAT GGT 7117 Arg Ser Pro Ala GluVal Asn Asn Asn Pro Cys Leu Glu Asn Asn Gly 6995 7000 7005 GGG TGC TCTCAT CTC TGC TTT GCT CTG CCT GGA TTG CAC ACC CCA AAA 7165 Gly Cys Ser HisLeu Cys Phe Ala Leu Pro Gly Leu His Thr Pro Lys 7010 7015 7020 TGT GACTGT GCC TTT GGG ACC CTG CAA AGT GAT GGC AAG AAT TGT GCC 7213 Cys Asp CysAla Phe Gly Thr Leu Gln Ser Asp Gly Lys Asn Cys Ala 7025 7030 7035 ATTTCA ACA GAA AAT TTC CTC ATC TTT GCC TTG TCT AAT TCC TTG AGA 7261 Ile SerThr Glu Asn Phe Leu Ile Phe Ala Leu Ser Asn Ser Leu Arg 7040 7045 70507055 AGC TTA CAC TTG GAC CCT GAA AAC CAT AGC CCA CCT TTC CAA ACA ATA7309 Ser Leu His Leu Asp Pro Glu Asn His Ser Pro Pro Phe Gln Thr Ile7060 7065 7070 AAT GTG GAA AGA ACT GTC ATG TCT CTA GAC TAT GAC AGT GTAAGT GAT 7357 Asn Val Glu Arg Thr Val Met Ser Leu Asp Tyr Asp Ser Val SerAsp 7075 7080 7085 AGA ATC TAC TTC ACA CAA AAT TTA GCC TCT GGA GTT GGACAG ATT TCC 7405 Arg Ile Tyr Phe Thr Gln Asn Leu Ala Ser Gly Val Gly GlnIle Ser 7090 7095 7100 TAT GCC ACC CTG TCT TCA GGG ATC CAT ACT CCA ACTGTC ATT GCT TCA 7453 Tyr Ala Thr Leu Ser Ser Gly Ile His Thr Pro Thr ValIle Ala Ser 7105 7110 7115 GGT ATA GGG ACT GCT GAT GGC ATT GCC TTT GACTGG ATT ACT AGA AGA 7501 Gly Ile Gly Thr Ala Asp Gly Ile Ala Phe Asp TrpIle Thr Arg Arg 7120 7125 7130 7135 ATT TAT TAC AGT GAC TAC CTC AAC CAGATG ATT AAT TCC ATG GCT GAA 7549 Ile Tyr Tyr Ser Asp Tyr Leu Asn Gln MetIle Asn Ser Met Ala Glu 7140 7145 7150 GAT GGG TCT AAC CGC ACT GTG ATAGCC CGC GTT CCA AAA CCA AGA GCA 7597 Asp Gly Ser Asn Arg Thr Val Ile AlaArg Val Pro Lys Pro Arg Ala 7155 7160 7165 ATT GTG TTA GAT CCC TGC CAAGGG TAC CTG TAC TGG GCT GAC TGG GAT 7645 Ile Val Leu Asp Pro Cys Gln GlyTyr Leu Tyr Trp Ala Asp Trp Asp 7170 7175 7180 ACA CAT GCC AAA ATC GAGAGA GCC ACA TTG GGA GGA AAC TTC CGC GTA 7693 Thr His Ala Lys Ile Glu ArgAla Thr Leu Gly Gly Asn Phe Arg Val 7185 7190 7195 CCC ATT GTG AAC AGCAGT CTG GTC ATG CCC AGT GGG CTG ACT CTG GAC 7741 Pro Ile Val Asn Ser SerLeu Val Met Pro Ser Gly Leu Thr Leu Asp 7200 7205 7210 7215 TAT GAA GAGGAC CTT CTC TAC TGG GTG GAT GCT AGT CTG CAG AGG ATT 7789 Tyr Glu Glu AspLeu Leu Tyr Trp Val Asp Ala Ser Leu Gln Arg Ile 7220 7225 7230 GAA CGCAGC ACT CTG ACG GGC GTG GAT CGT GAA GTC ATT GTC AAT GCA 7837 Glu Arg SerThr Leu Thr Gly Val Asp Arg Glu Val Ile Val Asn Ala 7235 7240 7245 GCCGTT CAT GCT TTT GGC TTG ACT CTC TAT GGC CAG TAT ATT TAC TGG 7885 Ala ValHis Ala Phe Gly Leu Thr Leu Tyr Gly Gln Tyr Ile Tyr Trp 7250 7255 7260ACT GAC TTG TAC ACA CAA AGA ATT TAC CGA GCT AAC AAA TAT GAC GGG 7933 ThrAsp Leu Tyr Thr Gln Arg Ile Tyr Arg Ala Asn Lys Tyr Asp Gly 7265 72707275 TCA GGT CAG ATT GCA ATG ACC ACA AAT TTG CTC TCC CAG CCC AGG GGA7981 Ser Gly Gln Ile Ala Met Thr Thr Asn Leu Leu Ser Gln Pro Arg Gly7280 7285 7290 7295 ATC AAC ACT GTT GTG AAG AAC CAG AAA CAA CAG TGT AACAAT CCT TGT 8029 Ile Asn Thr Val Val Lys Asn Gln Lys Gln Gln Cys Asn AsnPro Cys 7300 7305 7310 GAA CAG TTT AAT GGG GGC TGC AGC CAT ATC TGT GCACCA GGT CCA AAT 8077 Glu Gln Phe Asn Gly Gly Cys Ser His Ile Cys Ala ProGly Pro Asn 7315 7320 7325 GGT GCC GAG TGC CAG TGT CCA CAT GAG GGC AACTGG TAT TTG GCC AAC 8125 Gly Ala Glu Cys Gln Cys Pro His Glu Gly Asn TrpTyr Leu Ala Asn 7330 7335 7340 AAC AGG AAG CAC TGC ATT GTG GAC AAT GGTGAA CGA TGT GGT GCA TCT 8173 Asn Arg Lys His Cys Ile Val Asp Asn Gly GluArg Cys Gly Ala Ser 7345 7350 7355 TCC TTC ACC TGC TCC AAT GGG CGC TGCATC TCG GAA GAG TGG AAG TGT 8221 Ser Phe Thr Cys Ser Asn Gly Arg Cys IleSer Glu Glu Trp Lys Cys 7360 7365 7370 7375 GAT AAT GAC AAC GAC TGT GGGGAT GGC AGT GAT GAG ATG GAA AGT GTC 8269 Asp Asn Asp Asn Asp Cys Gly AspGly Ser Asp Glu Met Glu Ser Val 7380 7385 7390 TGT GCA CTT CAC ACC TGCTCA CCG ACA GCC TTC ACC TGT GCC AAT GGG 8317 Cys Ala Leu His Thr Cys SerPro Thr Ala Phe Thr Cys Ala Asn Gly 7395 7400 7405 CGA TGT GTC CAA TACTCT TAC CGC TGT GAT TAC TAC AAT GAC TGT GGT 8365 Arg Cys Val Gln Tyr SerTyr Arg Cys Asp Tyr Tyr Asn Asp Cys Gly 7410 7415 7420 GAT GGC AGT GATGAG GCA GGG TGC CTG TTC AGG GAC TGC AAT GCC ACC 8413 Asp Gly Ser Asp GluAla Gly Cys Leu Phe Arg Asp Cys Asn Ala Thr 7425 7430 7435 ACG GAG TTTATG TGC AAT AAC AGA AGG TGC ATA CCT CGT GAG TTT ATC 8461 Thr Glu Phe MetCys Asn Asn Arg Arg Cys Ile Pro Arg Glu Phe Ile 7440 7445 7450 7455 TGCAAT GGT GTA GAC AAC TGC CAT GAT AAT AAC ACT TCA GAT GAG AAA 8509 Cys AsnGly Val Asp Asn Cys His Asp Asn Asn Thr Ser Asp Glu Lys 7460 7465 7470AAT TGC CCT GAT CGC ACT TGC CAG TCT GGA TAC ACA AAA TGT CAT AAT 8557 AsnCys Pro Asp Arg Thr Cys Gln Ser Gly Tyr Thr Lys Cys His Asn 7475 74807485 TCA AAT ATT TGT ATT CCT CGC GTT TAT TTG TGT GAC GGA GAC AAT GAC8605 Ser Asn Ile Cys Ile Pro Arg Val Tyr Leu Cys Asp Gly Asp Asn Asp7490 7495 7500 TGT GGA GAT AAC AGT GAT GAA AAC CCT ACT TAT TGC ACC ACTCAC ACG 8653 Cys Gly Asp Asn Ser Asp Glu Asn Pro Thr Tyr Cys Thr Thr HisThr 7505 7510 7515 TGC AGC AGC AGT GAG TTC CAA TGC GCA TCT GGG CGC TGTATT CCT CAA 8701 Cys Ser Ser Ser Glu Phe Gln Cys Ala Ser Gly Arg Cys IlePro Gln 7520 7525 7530 7535 CAT TGG TAT TGT GAT CAA GAA ACA GAT TGT TTTGAT GCC TCT GAT GAA 8749 His Trp Tyr Cys Asp Gln Glu Thr Asp Cys Phe AspAla Ser Asp Glu 7540 7545 7550 CCT GCC TCT TGT GGT CAC TCT GAG CGA ACATGC CTA GCT GAT GAG TTC 8797 Pro Ala Ser Cys Gly His Ser Glu Arg Thr CysLeu Ala Asp Glu Phe 7555 7560 7565 AAG TGT GAT GGT GGG AGG TGC ATC CCAAGC GAA TGG ATC TGT GAC GGT 8845 Lys Cys Asp Gly Gly Arg Cys Ile Pro SerGlu Trp Ile Cys Asp Gly 7570 7575 7580 GAT AAT GAC TGT GGG GAT ATG AGTGAC GAG GAT AAA AGG CAC CAG TGT 8893 Asp Asn Asp Cys Gly Asp Met Ser AspGlu Asp Lys Arg His Gln Cys 7585 7590 7595 CAG AAT CAA AAC TGC TCG GATTCC GAG TTT CTC TGT GTA AAT GAC AGA 8941 Gln Asn Gln Asn Cys Ser Asp SerGlu Phe Leu Cys Val Asn Asp Arg 7600 7605 7610 7615 CCT CCG GAC AGG AGGTGC ATT CCC CAG TCT TGG GTC TGT GAT GGC GAT 8989 Pro Pro Asp Arg Arg CysIle Pro Gln Ser Trp Val Cys Asp Gly Asp 7620 7625 7630 GTG GAT TGT ACTGAC GGC TAC GAT GAG AAT CAG AAT TGC ACC AGG AGA 9037 Val Asp Cys Thr AspGly Tyr Asp Glu Asn Gln Asn Cys Thr Arg Arg 7635 7640 7645 ACT TGC TCTGAA AAT GAA TTC ACC TGT GGT TAC GGA CTG TGT ATC CCA 9085 Thr Cys Ser GluAsn Glu Phe Thr Cys Gly Tyr Gly Leu Cys Ile Pro 7650 7655 7660 AAG ATATTC AGG TGT GAC CGG CAC AAT GAC TGT GGT GAC TAT AGC GAC 9133 Lys Ile PheArg Cys Asp Arg His Asn Asp Cys Gly Asp Tyr Ser Asp 7665 7670 7675 GAGAGG GGC TGC TTA TAC CAG ACT TGC CAA CAG AAT CAG TTT ACC TGT 9181 Glu ArgGly Cys Leu Tyr Gln Thr Cys Gln Gln Asn Gln Phe Thr Cys 7680 7685 76907695 CAG AAC GGG CGC TGC ATT AGT AAA ACC TTC GTC TGT GAT GAG GAT AAT9229 Gln Asn Gly Arg Cys Ile Ser Lys Thr Phe Val Cys Asp Glu Asp Asn7700 7705 7710 GAC TGT GGA GAC GGA TCT GAT GAG CTG ATG CAC CTG TGC CACACC CCA 9277 Asp Cys Gly Asp Gly Ser Asp Glu Leu Met His Leu Cys His ThrPro 7715 7720 7725 GAA CCC ACG TGT CCA CCT CAC GAG TTC AAG TGT GAC AATGGG CGC TGC 9325 Glu Pro Thr Cys Pro Pro His Glu Phe Lys Cys Asp Asn GlyArg Cys 7730 7735 7740 ATC GAG ATG ATG AAA CTC TGC AAC CAC CTA GAT GACTGT TTG GAC AAC 9373 Ile Glu Met Met Lys Leu Cys Asn His Leu Asp Asp CysLeu Asp Asn 7745 7750 7755 AGC GAT GAG AAA GGC TGT GGC ATT AAT GAA TGCCAT GAC CCT TCA ATC 9421 Ser Asp Glu Lys Gly Cys Gly Ile Asn Glu Cys HisAsp Pro Ser Ile 7760 7765 7770 7775 AGT GGC TGC GAT CAC AAC TGC ACA GACACC TTA ACC AGT TTC TAT TGT 9469 Ser Gly Cys Asp His Asn Cys Thr Asp ThrLeu Thr Ser Phe Tyr Cys 7780 7785 7790 TCC TGT CGT CCT GGT TAC AAG CTCATG TCT GAC AAG CGG ACT TGT GTT 9517 Ser Cys Arg Pro Gly Tyr Lys Leu MetSer Asp Lys Arg Thr Cys Val 7795 7800 7805 GAT ATT GAT GAA TGC ACA GAGATG CCT TTT GTC TGT AGC CAG AAG TGT 9565 Asp Ile Asp Glu Cys Thr Glu MetPro Phe Val Cys Ser Gln Lys Cys 7810 7815 7820 GAG AAT GTA ATA GGC TCCTAC ATC TGT AAG TGT GCC CCA GGC TAC CTC 9613 Glu Asn Val Ile Gly Ser TyrIle Cys Lys Cys Ala Pro Gly Tyr Leu 7825 7830 7835 CGA GAA CCA GAT GGAAAG ACC TGC CGG CAA AAC AGT AAC ATC GAA CCC 9661 Arg Glu Pro Asp Gly LysThr Cys Arg Gln Asn Ser Asn Ile Glu Pro 7840 7845 7850 7855 TAT CTC ATTTTT AGC AAC CGT TAC TAT TTG AGA AAT TTA ACT ATA GAT 9709 Tyr Leu Ile PheSer Asn Arg Tyr Tyr Leu Arg Asn Leu Thr Ile Asp 7860 7865 7870 GGC TATTTT TAC TCC CTC ATC TTG GAA GGA CTG GAC AAT GTT GTG GCA 9757 Gly Tyr PheTyr Ser Leu Ile Leu Glu Gly Leu Asp Asn Val Val Ala 7875 7880 7885 TTAGAT TTT GAC CGA GTA GAG AAG AGA TTG TAT TGG ATT GAT ACA CAG 9805 Leu AspPhe Asp Arg Val Glu Lys Arg Leu Tyr Trp Ile Asp Thr Gln 7890 7895 7900AGG CAA GTC ATT GAG AGA ATG TTT CTG AAT AAG ACA AAC AAG GAG ACA 9853 ArgGln Val Ile Glu Arg Met Phe Leu Asn Lys Thr Asn Lys Glu Thr 7905 79107915 ATC ATA AAC CAC AGA CTA CCA GCT GCA GAA AGT CTG GCT GTA GAC TGG9901 Ile Ile Asn His Arg Leu Pro Ala Ala Glu Ser Leu Ala Val Asp Trp7920 7925 7930 7935 GTT TCC AGA AAG CTC TAC TGG TTG GAT GCC CGC CTG GATGGC CTC TTT 9949 Val Ser Arg Lys Leu Tyr Trp Leu Asp Ala Arg Leu Asp GlyLeu Phe 7940 7945 7950 GTC TCT GAC CTC AAT GGT GGA CAC CGC CGC ATG CTGGCC CAG CAC TGT 9997 Val Ser Asp Leu Asn Gly Gly His Arg Arg Met Leu AlaGln His Cys 7955 7960 7965 GTG GAT GCC AAC AAC ACC TTC TGC TTT GAT AATCCC AGA GGA CTT GCC 10045 Val Asp Ala Asn Asn Thr Phe Cys Phe Asp AsnPro Arg Gly Leu Ala 7970 7975 7980 CTT CAC CCT CAA TAT GGG TAC CTC TACTGG GCA GAC TGG GGT CAC CGC 10093 Leu His Pro Gln Tyr Gly Tyr Leu TyrTrp Ala Asp Trp Gly His Arg 7985 7990 7995 GCA TAC ATT GGG AGA GTA GGCATG GAT GGA ACC AAC AAG TCT GTG ATA 10141 Ala Tyr Ile Gly Arg Val GlyMet Asp Gly Thr Asn Lys Ser Val Ile 8000 8005 8010 8015 ATC TCC ACC AAGTTA GAG TGG CCT AAT GGC ATC ACC ATT GAT TAC ACC 10189 Ile Ser Thr LysLeu Glu Trp Pro Asn Gly Ile Thr Ile Asp Tyr Thr 8020 8025 8030 AAT GATCTA CTC TAC TGG GCA GAT GCC CAC CTG GGT TAC ATA GAG TAC 10237 Asn AspLeu Leu Tyr Trp Ala Asp Ala His Leu Gly Tyr Ile Glu Tyr 8035 8040 8045TCT GAT TTG GAG GGC CAC CAT CGA CAC ACG GTG TAT GAT GGG GCA CTG 10285Ser Asp Leu Glu Gly His His Arg His Thr Val Tyr Asp Gly Ala Leu 80508055 8060 CCT CAC CCT TTC GCT ATT ACC ATT TTT GAA GAC ACT ATT TAT TGGACA 10333 Pro His Pro Phe Ala Ile Thr Ile Phe Glu Asp Thr Ile Tyr TrpThr 8065 8070 8075 GAT TGG AAT ACA AGG ACA GTG GAA AAG GGA AAC AAA TATGAT GGA TCA 10381 Asp Trp Asn Thr Arg Thr Val Glu Lys Gly Asn Lys TyrAsp Gly Ser 8080 8085 8090 8095 AAT AGA CAG ACA CTG GTG AAC ACA ACA CACAGA CCA TTT GAC ATC CAT 10429 Asn Arg Gln Thr Leu Val Asn Thr Thr HisArg Pro Phe Asp Ile His 8100 8105 8110 GTG TAC CAT CCA TAT AGG CAG CCCATT GTG AGC AAT CCC TGT GGT ACC 10477 Val Tyr His Pro Tyr Arg Gln ProIle Val Ser Asn Pro Cys Gly Thr 8115 8120 8125 AAC AAT GGT GGC TGT TCTCAT CTC TGC CTC ATC AAG CCA GGA GGA AAA 10525 Asn Asn Gly Gly Cys SerHis Leu Cys Leu Ile Lys Pro Gly Gly Lys 8130 8135 8140 GGG TTC ACT TGCGAG TGT CCA GAT GAC TTC CGC ACC CTT CAA CTG AGT 10573 Gly Phe Thr CysGlu Cys Pro Asp Asp Phe Arg Thr Leu Gln Leu Ser 8145 8150 8155 GGC AGCACC TAC TGC ATG CCC ATG TGC TCC AGC ACC CAG TTC CTG TGC 10621 Gly SerThr Tyr Cys Met Pro Met Cys Ser Ser Thr Gln Phe Leu Cys 8160 8165 81708175 GCT AAC AAT GAA AAG TGC ATT CCT ATC TGG TGG AAA TGT GAT GGA CAG10669 Ala Asn Asn Glu Lys Cys Ile Pro Ile Trp Trp Lys Cys Asp Gly Gln8180 8185 8190 AAA GAC TGC TCA GAT GGC TCT GAT GAA CTG GCC CTT TGC CCGCAG CGC 10717 Lys Asp Cys Ser Asp Gly Ser Asp Glu Leu Ala Leu Cys ProGln Arg 8195 8200 8205 TTC TGC CGA CTG GGA CAG TTC CAG TGC AGT GAC GGCAAC TGC ACC AGC 10765 Phe Cys Arg Leu Gly Gln Phe Gln Cys Ser Asp GlyAsn Cys Thr Ser 8210 8215 8220 CCG CAG ACT TTA TGC AAT GCT CAC CAA AATTGC CCT GAT GGG TCT GAT 10813 Pro Gln Thr Leu Cys Asn Ala His Gln AsnCys Pro Asp Gly Ser Asp 8225 8230 8235 GAA GAC CGT CTT CTT TGT GAG AATCAC CAC TGT GAC TCC AAT GAA TGG 10861 Glu Asp Arg Leu Leu Cys Glu AsnHis His Cys Asp Ser Asn Glu Trp 8240 8245 8250 8255 CAG TGC GCC AAC AAACGT TGC ATC CCA GAA TCC TGG CAG TGT GAC ACA 10909 Gln Cys Ala Asn LysArg Cys Ile Pro Glu Ser Trp Gln Cys Asp Thr 8260 8265 8270 TTT AAC GACTGT GAG GAT AAC TCA GAT GAA GAC AGT TCC CAC TGT GCC 10957 Phe Asn AspCys Glu Asp Asn Ser Asp Glu Asp Ser Ser His Cys Ala 8275 8280 8285 AGCAGG ACC TGC CGG CCG GGC CAG TTT CGG TGT GCT AAT GGC CGC TGC 11005 SerArg Thr Cys Arg Pro Gly Gln Phe Arg Cys Ala Asn Gly Arg Cys 8290 82958300 ATC CCG CAG GCC TGG AAG TGT GAT GTG GAT AAT GAT TGT GGA GAC CAC11053 Ile Pro Gln Ala Trp Lys Cys Asp Val Asp Asn Asp Cys Gly Asp His8305 8310 8315 TCG GAT GAG CCC ATT GAA GAA TGC ATG AGC TCT GCC CAT CTCTGT GAC 11101 Ser Asp Glu Pro Ile Glu Glu Cys Met Ser Ser Ala His LeuCys Asp 8320 8325 8330 8335 AAC TTC ACA GAA TTC AGC TGC AAA ACA AAT TACCGC TGC ATC CCA AAG 11149 Asn Phe Thr Glu Phe Ser Cys Lys Thr Asn TyrArg Cys Ile Pro Lys 8340 8345 8350 TGG GCC GTG TGC AAT GGT GTA GAT GACTGC AGG GAC AAC AGT GAT GAG 11197 Trp Ala Val Cys Asn Gly Val Asp AspCys Arg Asp Asn Ser Asp Glu 8355 8360 8365 CAA GGC TGT GAG GAG AGG ACATGC CAT CCT GTG GGG GAT TTC CGC TGT 11245 Gln Gly Cys Glu Glu Arg ThrCys His Pro Val Gly Asp Phe Arg Cys 8370 8375 8380 AAA AAT CAC CAC TGCATC CCT CTT CGT TGG CAG TGT GAT GGG CAA AAT 11293 Lys Asn His His CysIle Pro Leu Arg Trp Gln Cys Asp Gly Gln Asn 8385 8390 8395 GAC TGT GGAGAT AAC TCA GAT GAG GAA AAC TGT GCT CCC CGG GAG TGC 11341 Asp Cys GlyAsp Asn Ser Asp Glu Glu Asn Cys Ala Pro Arg Glu Cys 8400 8405 8410 8415ACA GAG AGC GAG TTT CGA TGT GTC AAT CAG CAG TGC ATT CCC TCG CGA 11389Thr Glu Ser Glu Phe Arg Cys Val Asn Gln Gln Cys Ile Pro Ser Arg 84208425 8430 TGG ATC TGT GAC CAT TAC AAC GAC TGT GGG GAC AAC TCA GAT GAACGG 11437 Trp Ile Cys Asp His Tyr Asn Asp Cys Gly Asp Asn Ser Asp GluArg 8435 8440 8445 GAC TGT GAG ATG AGG ACC TGC CAT CCT GAA TAT TTT CAGTGT ACA AGT 11485 Asp Cys Glu Met Arg Thr Cys His Pro Glu Tyr Phe GlnCys Thr Ser 8450 8455 8460 GGA CAT TGT GTA CAC AGT GAA CTG AAA TGC GATGGA TCC GCT GAC TGT 11533 Gly His Cys Val His Ser Glu Leu Lys Cys AspGly Ser Ala Asp Cys 8465 8470 8475 TTG GAT GCG TCT GAT GAA GCT GAT TGTCCC ACA CGC TTT CCT GAT GGT 11581 Leu Asp Ala Ser Asp Glu Ala Asp CysPro Thr Arg Phe Pro Asp Gly 8480 8485 8490 8495 GCA TAC TGC CAG GCT ACTATG TTC GAA TGC AAA AAC CAT GTT TGT ATC 11629 Ala Tyr Cys Gln Ala ThrMet Phe Glu Cys Lys Asn His Val Cys Ile 8500 8505 8510 CCG CCA TAT TGGAAA TGT GAT GGC GAT GAT GAC TGT GGC GAT GGT TCA 11677 Pro Pro Tyr TrpLys Cys Asp Gly Asp Asp Asp Cys Gly Asp Gly Ser 8515 8520 8525 GAT GAAGAA CTT CAC CTG TGC TTG GAT GTT CCC TGT AAT TCA CCA AAC 11725 Asp GluGlu Leu His Leu Cys Leu Asp Val Pro Cys Asn Ser Pro Asn 8530 8535 8540CGT TTC CGG TGT GAC AAC AAT CGC TGC ATT TAT AGT CAT GAG GTG TGC 11773Arg Phe Arg Cys Asp Asn Asn Arg Cys Ile Tyr Ser His Glu Val Cys 85458550 8555 AAT GGT GTG GAT GAC TGT GGA GAT GGA ACT GAT GAG ACA GAG GAGCAC 11821 Asn Gly Val Asp Asp Cys Gly Asp Gly Thr Asp Glu Thr Glu GluHis 8560 8565 8570 8575 TGT AGA AAA CCG ACC CCT AAA CCT TGT ACA GAA TATGAA TAT AAG TGT 11869 Cys Arg Lys Pro Thr Pro Lys Pro Cys Thr Glu TyrGlu Tyr Lys Cys 8580 8585 8590 GGC AAT GGG CAT TGC ATT CCA CAT GAC AATGTG TGT GAT GAT GCC GAT 11917 Gly Asn Gly His Cys Ile Pro His Asp AsnVal Cys Asp Asp Ala Asp 8595 8600 8605 GAC TGT GGT GAC TGG TCC GAT GAACTG GGT TGC AAT AAA GGA AAA GAA 11965 Asp Cys Gly Asp Trp Ser Asp GluLeu Gly Cys Asn Lys Gly Lys Glu 8610 8615 8620 AGA ACA TGT GCT GAA AATATA TGC GAG CAA AAT TGT ACC CAA TTA AAT 12013 Arg Thr Cys Ala Glu AsnIle Cys Glu Gln Asn Cys Thr Gln Leu Asn 8625 8630 8635 GAA GGA GGA TTTATC TGC TCC TGT ACA GCT GGG TTC GAA ACC AAT GTT 12061 Glu Gly Gly PheIle Cys Ser Cys Thr Ala Gly Phe Glu Thr Asn Val 8640 8645 8650 8655 TTTGAC AGA ACC TCC TGT CTA GAT ATC AAT GAA TGT GAA CAA TTT GGG 12109 PheAsp Arg Thr Ser Cys Leu Asp Ile Asn Glu Cys Glu Gln Phe Gly 8660 86658670 ACT TGT CCC CAG CAC TGC AGA AAT ACC AAA GGA AGT TAT GAG TGT GTC12157 Thr Cys Pro Gln His Cys Arg Asn Thr Lys Gly Ser Tyr Glu Cys Val8675 8680 8685 TGT GCT GAT GGC TTC ACG TCT ATG AGT GAC CGC CCT GGA AAACGA TGT 12205 Cys Ala Asp Gly Phe Thr Ser Met Ser Asp Arg Pro Gly LysArg Cys 8690 8695 8700 GCA GCT GAG GGT AGC TCT CCT TTG TTG CTA CTG CCTGAC AAT GTC CGA 12253 Ala Ala Glu Gly Ser Ser Pro Leu Leu Leu Leu ProAsp Asn Val Arg 8705 8710 8715 ATT CGA AAA TAT AAT CTC TCA TCT GAG AGGTTC TCA GAG TAT CTT CAA 12301 Ile Arg Lys Tyr Asn Leu Ser Ser Glu ArgPhe Ser Glu Tyr Leu Gln 8720 8725 8730 8735 GAT GAG GAA TAT ATC CAA GCTGTT GAT TAT GAT TGG GAT CCC GAG GAC 12349 Asp Glu Glu Tyr Ile Gln AlaVal Asp Tyr Asp Trp Asp Pro Glu Asp 8740 8745 8750 ATA GGC CTC AGT GTTGTG TAT TAC ACT GTG CGA GGG GAG GGC TCT AGG 12397 Ile Gly Leu Ser ValVal Tyr Tyr Thr Val Arg Gly Glu Gly Ser Arg 8755 8760 8765 TTT GGT GCTATC AAA CGT GCC TAC ATC CCC AAC TTT GAA TCC GGC CGC 12445 Phe Gly AlaIle Lys Arg Ala Tyr Ile Pro Asn Phe Glu Ser Gly Arg 8770 8775 8780 AATAAT CTT GTG CAG GAA GTT GAC CTG AAA CTG AAA TAC GTA ATG CAG 12493 AsnAsn Leu Val Gln Glu Val Asp Leu Lys Leu Lys Tyr Val Met Gln 8785 87908795 CCA GAT GGA ATA GCA GTG GAC TGG GTT GGA AGG CAT ATT TAC TGG TCA12541 Pro Asp Gly Ile Ala Val Asp Trp Val Gly Arg His Ile Tyr Trp Ser8800 8805 8810 8815 GAT GTC AAG AAT AAA CGC ATT GAG GTG GCT AAA CTT GATGGA AGG TAC 12589 Asp Val Lys Asn Lys Arg Ile Glu Val Ala Lys Leu AspGly Arg Tyr 8820 8825 8830 AGA AAG TGG CTG ATT TCC ACT GAC CTG GAC CAACCA GCT GCT ATT GCT 12637 Arg Lys Trp Leu Ile Ser Thr Asp Leu Asp GlnPro Ala Ala Ile Ala 8835 8840 8845 GTG AAT CCC AAA CTA GGG CTT ATG TTCTGG ACT GAC TGG GGA AAG GAA 12685 Val Asn Pro Lys Leu Gly Leu Met PheTrp Thr Asp Trp Gly Lys Glu 8850 8855 8860 CCT AAA CTC GAG TCT GCC TGGATG AAT GGA GAG GAC CGC AAC ATC CTG 12733 Pro Lys Leu Glu Ser Ala TrpMet Asn Gly Glu Asp Arg Asn Ile Leu 8865 8870 8875 GTT TTC GAG GAC CTTGGT TGG CCA ACT GGC CTT TCT ATC GAT TAT TTG 12781 Val Phe Glu Asp LeuGly Trp Pro Thr Gly Leu Ser Ile Asp Tyr Leu 8880 8885 8890 8895 AAC AATGAC CGA ATC TAC TGG AGT GAC TTC AAG GAG GAC GTT ATT GAA 12829 Asn AsnAsp Arg Ile Tyr Trp Ser Asp Phe Lys Glu Asp Val Ile Glu 8900 8905 8910ACC ATA AAA TAT GAT GGG ACT GAT AGG AGA GTC ATT GCA AAG GAA GCA 12877Thr Ile Lys Tyr Asp Gly Thr Asp Arg Arg Val Ile Ala Lys Glu Ala 89158920 8925 ATG AAC CCT TAC AGC CTG GAC ATC TTT GAA GAC CAG TTA TAC TGGATA 12925 Met Asn Pro Tyr Ser Leu Asp Ile Phe Glu Asp Gln Leu Tyr TrpIle 8930 8935 8940 TCT AAG GAA AAG GGA GAA GTA TGG AAA CAA AAT AAA TTTGGG CAA GGA 12973 Ser Lys Glu Lys Gly Glu Val Trp Lys Gln Asn Lys PheGly Gln Gly 8945 8950 8955 AAG AAA GAG AAA ACG CTG GTA GTG AAC CCT TGGCTC ACT CAA GTT CGA 13021 Lys Lys Glu Lys Thr Leu Val Val Asn Pro TrpLeu Thr Gln Val Arg 8960 8965 8970 8975 ATC TTT CAT CAA CTC AGA TAC AATAAG TCA GTG CCC AAC CTT TGC AAA 13069 Ile Phe His Gln Leu Arg Tyr AsnLys Ser Val Pro Asn Leu Cys Lys 8980 8985 8990 CAG ATC TGC AGC CAC CTCTGC CTT CTG AGA CCT GGA GGA TAC AGC TGT 13117 Gln Ile Cys Ser His LeuCys Leu Leu Arg Pro Gly Gly Tyr Ser Cys 8995 9000 9005 GCC TGT CCC CAAGGC TCC AGC TTT ATA GAG GGG AGC ACC ACT GAG TGT 13165 Ala Cys Pro GlnGly Ser Ser Phe Ile Glu Gly Ser Thr Thr Glu Cys 9010 9015 9020 GAT GCAGCC ATT GAA CTG CCT ATC AAC CTG CCC CCC CCA TGC AGG TGC 13213 Asp AlaAla Ile Glu Leu Pro Ile Asn Leu Pro Pro Pro Cys Arg Cys 9025 9030 9035ATG CAC GGA GGA AAT TGC TAT TTT GAT GAG ACT GAC CTC CCC AAA TGC 13261Met His Gly Gly Asn Cys Tyr Phe Asp Glu Thr Asp Leu Pro Lys Cys 90409045 9050 9055 AAG TGT CCT AGC GGC TAC ACC GGA AAA TAT TGT GAA ATG GCGTTT TCA 13309 Lys Cys Pro Ser Gly Tyr Thr Gly Lys Tyr Cys Glu Met AlaPhe Ser 9060 9065 9070 AAA GGC ATC TCT CCA GGA ACA ACC GCA GTA GCT GTGCTG TTG ACA ATC 13357 Lys Gly Ile Ser Pro Gly Thr Thr Ala Val Ala ValLeu Leu Thr Ile 9075 9080 9085 CTC TTG ATC GTC GTA ATT GGA GCT CTG GCAATT GCA GGA TTC TTC CAC 13405 Leu Leu Ile Val Val Ile Gly Ala Leu AlaIle Ala Gly Phe Phe His 9090 9095 9100 TAT AGA AGG ACC GGC TCC CTT TTGCCT GCT CTG CCC AAG CTG CCA AGC 13453 Tyr Arg Arg Thr Gly Ser Leu LeuPro Ala Leu Pro Lys Leu Pro Ser 9105 9110 9115 TTA AGC AGT CTC GTC AAGCCC TCT GAA AAT GGG AAT GGG GTG ACC TTC 13501 Leu Ser Ser Leu Val LysPro Ser Glu Asn Gly Asn Gly Val Thr Phe 9120 9125 9130 9135 AGA TCA GGGGCA GAT CTT AAC ATG GAT ATT GGA GTG TCT GGT TTT GGA 13549 Arg Ser GlyAla Asp Leu Asn Met Asp Ile Gly Val Ser Gly Phe Gly 9140 9145 9150 CCTGAG ACT GCT ATT GAC AGG TCA ATG GCA ATG AGT GAA GAC TTT GTC 13597 ProGlu Thr Ala Ile Asp Arg Ser Met Ala Met Ser Glu Asp Phe Val 9155 91609165 ATG GAA ATG GGG AAG CAG CCC ATA ATA TTT GAA AAC CCA ATG TAC TCA13645 Met Glu Met Gly Lys Gln Pro Ile Ile Phe Glu Asn Pro Met Tyr Ser9170 9175 9180 GCC AGA GAC AGT GCT GTC AAA GTG GTT CAG CCA ATC CAG GTGACT GTA 13693 Ala Arg Asp Ser Ala Val Lys Val Val Gln Pro Ile Gln ValThr Val 9185 9190 9195 TCT GAA AAT GTG GAT AAT AAG AAT TAT GGA AGT CCCATA AAC CCT TCT 13741 Ser Glu Asn Val Asp Asn Lys Asn Tyr Gly Ser ProIle Asn Pro Ser 9200 9205 9210 9215 GAG ATA GTT CCA GAG ACA AAC CCA ACTTCA CCA GCT GCT GAT GGA ACT 13789 Glu Ile Val Pro Glu Thr Asn Pro ThrSer Pro Ala Ala Asp Gly Thr 9220 9225 9230 CAG GTG ACA AAA TGG AAT CTCTTC AAA CGA AAA TCT AAA CAA ACT ACC 13837 Gln Val Thr Lys Trp Asn LeuPhe Lys Arg Lys Ser Lys Gln Thr Thr 9235 9240 9245 AAC TTT GAA AAT CCAATC TAT GCA CAG ATG GAG AAC GAG CAA AAG GAA 13885 Asn Phe Glu Asn ProIle Tyr Ala Gln Met Glu Asn Glu Gln Lys Glu 9250 9255 9260 AGT GTT GCTGCG ACA CCA CCT CCA TCA CCT TCG CTC CCT GCT AAG CCT 13933 Ser Val AlaAla Thr Pro Pro Pro Ser Pro Ser Leu Pro Ala Lys Pro 9265 9270 9275 AAGCCT CCT TCG AGA AGA GAC CCA ACT CCA ACC TAT TCT GCA ACA GAA 13981 LysPro Pro Ser Arg Arg Asp Pro Thr Pro Thr Tyr Ser Ala Thr Glu 9280 92859290 9295 GAC ACT TTT AAA GAC ACC GCA AAT CTT GTT AAA GAA GAC TCT GAAGTA 14029 Asp Thr Phe Lys Asp Thr Ala Asn Leu Val Lys Glu Asp Ser GluVal 9300 9305 9310 TAG CTATACCAGC TA 14044 * 4655 amino acids amino acidlinear protein unknown 90 Met Asp Arg Gly Pro Ala Ala Val Ala Cys ThrLeu Leu Leu Ala Leu 1 5 10 15 Val Ala Cys Leu Ala Pro Ala Ser Gly GlnGlu Cys Asp Ser Ala His 20 25 30 Phe Arg Cys Gly Ser Gly His Cys Ile ProAla Asp Trp Arg Cys Asp 35 40 45 Gly Thr Lys Asp Cys Ser Asp Asp Ala AspGlu Ile Gly Cys Ala Val 50 55 60 Val Thr Cys Gln Gln Gly Tyr Phe Lys CysGln Ser Glu Gly Gln Cys 65 70 75 80 Ile Pro Ser Ser Trp Val Cys Asp GlnAsp Gln Asp Cys Asp Asp Gly 85 90 95 Ser Asp Glu Arg Gln Asp Cys Ser GlnSer Thr Cys Ser Ser His Gln 100 105 110 Ile Thr Cys Ser Asn Gly Gln CysIle Pro Ser Glu Tyr Arg Cys Asp 115 120 125 His Val Arg Asp Cys Pro AspGly Ala Asp Glu Asn Asp Cys Gln Tyr 130 135 140 Pro Thr Cys Glu Gln LeuThr Cys Asp Asn Gly Ala Cys Tyr Asn Thr 145 150 155 160 Ser Gln Lys CysAsp Trp Lys Val Asp Cys Arg Asp Ser Ser Asp Glu 165 170 175 Ile Asn CysThr Glu Ile Cys Leu His Asn Glu Phe Ser Cys Gly Asn 180 185 190 Gly GluCys Ile Pro Arg Ala Tyr Val Cys Asp His Asp Asn Asp Cys 195 200 205 GlnAsp Gly Ser Asp Glu His Ala Cys Asn Tyr Pro Thr Cys Gly Gly 210 215 220Tyr Gln Phe Thr Cys Pro Ser Gly Arg Cys Ile Tyr Gln Asn Trp Val 225 230235 240 Cys Asp Gly Glu Asp Asp Cys Lys Asp Asn Gly Asp Glu Asp Gly Cys245 250 255 Glu Ser Gly Pro His Asp Val His Lys Cys Ser Pro Arg Glu TrpSer 260 265 270 Cys Pro Glu Ser Gly Arg Cys Ile Ser Ile Tyr Lys Val CysAsp Gly 275 280 285 Ile Leu Asp Cys Pro Gly Arg Glu Asp Glu Asn Asn ThrSer Thr Gly 290 295 300 Lys Tyr Cys Ser Met Thr Leu Cys Ser Ala Leu AsnCys Gln Tyr Gln 305 310 315 320 Cys His Glu Thr Pro Tyr Gly Gly Ala CysPhe Cys Pro Pro Gly Tyr 325 330 335 Ile Ile Asn His Asn Asp Ser Arg ThrCys Val Glu Phe Asp Asp Cys 340 345 350 Gln Ile Trp Gly Ile Cys Asp GlnLys Cys Glu Ser Arg Pro Gly Arg 355 360 365 His Leu Cys His Cys Glu GluGly Tyr Ile Leu Glu Arg Gly Gln Tyr 370 375 380 Cys Lys Ala Asn Asp SerPhe Gly Glu Ala Ser Ile Ile Phe Ser Asn 385 390 395 400 Gly Arg Asp LeuLeu Ile Gly Asp Ile His Gly Arg Ser Phe Arg Ile 405 410 415 Leu Val GluSer Gln Asn Arg Gly Val Ala Val Gly Val Ala Phe His 420 425 430 Tyr HisLeu Gln Arg Val Phe Trp Thr Asp Thr Val Gln Asn Lys Val 435 440 445 PheSer Val Asp Ile Asn Gly Leu Asn Ile Gln Glu Val Leu Asn Val 450 455 460Ser Val Glu Thr Pro Glu Asn Leu Ala Val Asp Trp Val Asn Asn Lys 465 470475 480 Ile Tyr Leu Val Glu Thr Lys Val Asn Arg Ile Asp Met Val Asn Leu485 490 495 Asp Gly Ser Tyr Arg Val Thr Leu Ile Thr Glu Asn Leu Gly HisPro 500 505 510 Arg Gly Ile Ala Val Asp Pro Thr Val Gly Tyr Leu Phe PheSer Asp 515 520 525 Trp Glu Ser Leu Ser Gly Glu Pro Lys Leu Glu Arg AlaPhe Met Asp 530 535 540 Gly Ser Asn Arg Lys Asp Leu Val Lys Thr Lys LeuGly Trp Pro Ala 545 550 555 560 Gly Val Thr Leu Asp Met Ile Ser Lys ArgVal Tyr Trp Val Asp Ser 565 570 575 Arg Phe Asp Tyr Ile Glu Thr Val ThrTyr Asp Gly Ile Gln Arg Lys 580 585 590 Thr Val Val His Gly Gly Ser LeuIle Pro His Pro Phe Gly Val Ser 595 600 605 Leu Phe Glu Gly Gln Val PhePhe Thr Asp Trp Thr Lys Met Ala Val 610 615 620 Leu Lys Ala Asn Lys PheThr Glu Thr Asn Pro Gln Val Tyr Tyr Gln 625 630 635 640 Ala Ser Leu ArgPro Tyr Gly Val Thr Val Tyr His Ser Leu Arg Gln 645 650 655 Pro Tyr AlaThr Asn Pro Cys Lys Asp Asn Asn Gly Gly Cys Glu Gln 660 665 670 Val CysVal Leu Ser His Arg Thr Asp Asn Asp Gly Leu Gly Phe Arg 675 680 685 CysLys Cys Thr Phe Gly Phe Gln Leu Asp Thr Asp Glu Arg His Cys 690 695 700Ile Ala Val Gln Asn Phe Leu Ile Phe Ser Ser Gln Val Ala Ile Arg 705 710715 720 Gly Ile Pro Phe Thr Leu Ser Thr Gln Glu Asp Val Met Val Pro Val725 730 735 Ser Gly Asn Pro Ser Phe Phe Val Gly Ile Asp Phe Asp Ala GlnAsp 740 745 750 Ser Thr Ile Phe Phe Ser Asp Met Ser Lys His Met Ile PheLys Gln 755 760 765 Lys Ile Asp Gly Thr Gly Arg Glu Ile Leu Ala Ala AsnArg Val Glu 770 775 780 Asn Val Glu Ser Leu Ala Phe Asp Trp Ile Ser LysAsn Leu Tyr Trp 785 790 795 800 Thr Asp Ser His Tyr Lys Ser Ile Ser ValMet Arg Leu Ala Asp Lys 805 810 815 Thr Arg Arg Thr Val Val Gln Tyr LeuAsn Asn Pro Arg Ser Val Val 820 825 830 Val His Pro Phe Ala Gly Tyr LeuPhe Phe Thr Asp Trp Phe Arg Pro 835 840 845 Ala Lys Ile Met Arg Ala TrpSer Asp Gly Ser His Leu Leu Pro Val 850 855 860 Ile Asn Thr Thr Leu GlyTrp Pro Asn Gly Leu Ala Ile Asp Trp Ala 865 870 875 880 Ala Ser Arg LeuTyr Trp Val Asp Ala Tyr Phe Asp Lys Ile Glu His 885 890 895 Ser Thr PheAsp Gly Leu Asp Arg Arg Arg Leu Gly His Ile Glu Gln 900 905 910 Met ThrHis Pro Phe Gly Leu Ala Ile Phe Gly Glu His Leu Phe Phe 915 920 925 ThrAsp Trp Arg Leu Gly Ala Ile Ile Arg Val Arg Lys Ala Asp Gly 930 935 940Gly Glu Met Thr Val Ile Arg Ser Gly Ile Ala Tyr Ile Leu His Leu 945 950955 960 Lys Ser Tyr Asp Val Asn Ile Gln Thr Gly Ser Asn Ala Cys Asn Gln965 970 975 Pro Thr His Pro Asn Gly Asp Cys Ser His Phe Cys Phe Pro ValPro 980 985 990 Asn Phe Gln Arg Val Cys Gly Cys Pro Tyr Gly Met Arg LeuAla Ser 995 1000 1005 Asn His Leu Thr Cys Glu Gly Asp Pro Thr Asn GluPro Pro Thr Glu 1010 1015 1020 Gln Cys Gly Leu Phe Ser Phe Pro Cys LysAsn Gly Arg Cys Val Pro 1025 1030 1035 1040 Asn Tyr Tyr Leu Cys Asp GlyVal Asp Asp Cys His Asp Asn Ser Asp 1045 1050 1055 Glu Gln Leu Cys GlyThr Leu Asn Asn Thr Cys Ser Ser Ser Ala Phe 1060 1065 1070 Thr Cys GlyHis Gly Glu Cys Ile Pro Ala His Trp Arg Cys Asp Lys 1075 1080 1085 ArgAsn Asp Cys Val Asp Gly Ser Asp Glu His Asn Cys Pro Thr His 1090 10951100 Ala Pro Ala Ser Cys Leu Asp Thr Gln Tyr Thr Cys Asp Asn His Gln1105 1110 1115 1120 Cys Ile Ser Lys Asn Trp Val Cys Asp Thr Asp Asn AspCys Gly Asp 1125 1130 1135 Gly Ser Asp Glu Lys Asn Cys Asn Ser Thr GluThr Cys Gln Pro Ser 1140 1145 1150 Gln Phe Asn Cys Pro Asn His Arg CysIle Asp Leu Ser Phe Val Cys 1155 1160 1165 Asp Gly Asp Lys Asp Cys ValAsp Gly Ser Asp Glu Val Gly Cys Val 1170 1175 1180 Leu Asn Cys Thr AlaSer Gln Phe Lys Cys Ala Ser Gly Asp Lys Cys 1185 1190 1195 1200 Ile GlyVal Thr Asn Arg Cys Asp Gly Val Phe Asp Cys Ser Asp Asn 1205 1210 1215Ser Asp Glu Ala Gly Cys Pro Thr Arg Pro Pro Gly Met Cys His Ser 12201225 1230 Asp Glu Phe Gln Cys Gln Glu Asp Gly Ile Cys Ile Pro Asn PheTrp 1235 1240 1245 Glu Cys Asp Gly His Pro Asp Cys Leu Tyr Gly Ser AspGlu His Asn 1250 1255 1260 Ala Cys Val Pro Lys Thr Cys Pro Ser Ser TyrPhe His Cys Asp Asn 1265 1270 1275 1280 Gly Asn Cys Ile His Arg Ala TrpLeu Cys Asp Arg Asp Asn Asp Cys 1285 1290 1295 Gly Asp Met Ser Asp GluLys Asp Cys Pro Thr Gln Pro Phe Arg Cys 1300 1305 1310 Pro Ser Trp GlnTrp Gln Cys Leu Gly His Asn Ile Cys Val Asn Leu 1315 1320 1325 Ser ValVal Cys Asp Gly Ile Phe Asp Cys Pro Asn Gly Thr Asp Glu 1330 1335 1340Ser Pro Leu Cys Asn Gly Asn Ser Cys Ser Asp Phe Asn Gly Gly Cys 13451350 1355 1360 Thr His Glu Cys Val Gln Glu Pro Phe Gly Ala Lys Cys LeuCys Pro 1365 1370 1375 Leu Gly Phe Leu Leu Ala Asn Asp Ser Lys Thr CysGlu Asp Ile Asp 1380 1385 1390 Glu Cys Asp Ile Leu Gly Ser Cys Ser GlnHis Cys Tyr Asn Met Arg 1395 1400 1405 Gly Ser Phe Arg Cys Ser Cys AspThr Gly Tyr Met Leu Glu Ser Asp 1410 1415 1420 Gly Arg Thr Cys Lys ValThr Ala Ser Glu Ser Leu Leu Leu Leu Val 1425 1430 1435 1440 Ala Ser GlnAsn Lys Ile Ile Ala Asp Ser Val Thr Ser Gln Val His 1445 1450 1455 AsnIle Tyr Ser Leu Val Glu Asn Gly Ser Tyr Ile Val Ala Val Asp 1460 14651470 Phe Asp Ser Ile Ser Gly Arg Ile Phe Trp Ser Asp Ala Thr Gln Gly1475 1480 1485 Lys Thr Trp Ser Ala Phe Gln Asn Gly Thr Asp Arg Arg ValVal Phe 1490 1495 1500 Asp Ser Ser Ile Ile Leu Thr Glu Thr Ile Ala IleAsp Trp Val Gly 1505 1510 1515 1520 Arg Asn Leu Tyr Trp Thr Asp Tyr AlaLeu Glu Thr Ile Glu Val Ser 1525 1530 1535 Lys Ile Asp Gly Ser His ArgThr Val Leu Ile Ser Lys Asn Leu Thr 1540 1545 1550 Asn Pro Arg Gly LeuAla Leu Asp Pro Arg Met Asn Glu His Leu Leu 1555 1560 1565 Phe Trp SerAsp Trp Gly His His Pro Arg Ile Glu Arg Ala Ser Met 1570 1575 1580 AspGly Ser Met Arg Thr Val Ile Val Gln Asp Lys Ile Phe Trp Pro 1585 15901595 1600 Cys Gly Leu Thr Ile Asp Tyr Pro Asn Arg Leu Leu Tyr Phe MetAsp 1605 1610 1615 Ser Tyr Leu Asp Tyr Met Asp Phe Cys Asp Tyr Asn GlyHis His Arg 1620 1625 1630 Arg Gln Val Ile Ala Ser Asp Leu Ile Ile ArgHis Pro Tyr Ala Leu 1635 1640 1645 Thr Leu Phe Glu Asp Ser Val Tyr TrpThr Asp Arg Ala Thr Arg Arg 1650 1655 1660 Val Met Arg Ala Asn Lys TrpHis Gly Gly Asn Gln Ser Val Val Met 1665 1670 1675 1680 Tyr Asn Ile GlnTrp Pro Leu Gly Ile Val Ala Val His Pro Ser Lys 1685 1690 1695 Gln ProAsn Ser Val Asn Pro Cys Ala Phe Ser Arg Cys Ser His Leu 1700 1705 1710Cys Leu Leu Ser Ser Gln Gly Pro His Phe Tyr Ser Cys Val Cys Pro 17151720 1725 Ser Gly Trp Ser Leu Ser Pro Asp Leu Leu Asn Cys Leu Arg AspAsp 1730 1735 1740 Gln Pro Phe Leu Ile Thr Val Arg Gln His Ile Ile PheGly Ile Ser 1745 1750 1755 1760 Leu Asn Pro Glu Val Lys Ser Asn Asp AlaMet Val Pro Ile Ala Gly 1765 1770 1775 Ile Gln Asn Gly Leu Asp Val GluPhe Asp Asp Ala Glu Gln Tyr Ile 1780 1785 1790 Tyr Trp Val Glu Asn ProGly Glu Ile His Arg Val Lys Thr Asp Gly 1795 1800 1805 Thr Asn Arg ThrVal Phe Ala Ser Ile Ser Met Val Gly Pro Ser Met 1810 1815 1820 Asn LeuAla Leu Asp Trp Ile Ser Arg Asn Leu Tyr Ser Thr Asn Pro 1825 1830 18351840 Arg Thr Gln Ser Ile Glu Val Leu Thr Leu His Gly Asp Ile Arg Tyr1845 1850 1855 Arg Lys Thr Leu Ile Ala Asn Asp Gly Thr Ala Leu Gly ValGly Phe 1860 1865 1870 Pro Ile Gly Ile Thr Val Asp Pro Ala Arg Gly LysLeu Tyr Trp Ser 1875 1880 1885 Asp Gln Gly Thr Asp Ser Gly Val Pro AlaLys Ile Ala Ser Ala Asn 1890 1895 1900 Met Asp Gly Thr Ser Val Lys ThrLeu Phe Thr Gly Asn Leu Glu His 1905 1910 1915 1920 Leu Glu Cys Val ThrLeu Asp Ile Glu Glu Gln Lys Leu Tyr Trp Ala 1925 1930 1935 Val Thr GlyArg Gly Val Ile Glu Arg Gly Asn Val Asp Gly Thr Asp 1940 1945 1950 ArgMet Ile Leu Val His Gln Leu Ser His Pro Trp Gly Ile Ala Val 1955 19601965 His Asp Ser Phe Leu Tyr Tyr Thr Asp Glu Gln Tyr Glu Val Ile Glu1970 1975 1980 Arg Val Asp Lys Ala Thr Gly Ala Asn Lys Ile Val Leu ArgAsp Asn 1985 1990 1995 2000 Val Pro Asn Leu Arg Gly Leu Gln Val Tyr HisArg Arg Asn Ala Ala 2005 2010 2015 Glu Ser Ser Asn Gly Cys Ser Asn AsnMet Asn Ala Cys Gln Gln Ile 2020 2025 2030 Cys Leu Pro Val Pro Gly GlyLeu Phe Ser Cys Ala Cys Ala Thr Gly 2035 2040 2045 Phe Lys Leu Asn ProAsp Asn Arg Ser Cys Ser Pro Tyr Asn Ser Phe 2050 2055 2060 Ile Val ValSer Met Leu Ser Ala Ile Arg Gly Phe Ser Leu Glu Leu 2065 2070 2075 2080Ser Asp His Ser Glu Thr Met Val Pro Val Ala Gly Gln Gly Arg Asn 20852090 2095 Ala Leu His Val Asp Val Asp Val Ser Ser Gly Phe Ile Tyr TrpCys 2100 2105 2110 Asp Phe Ser Ser Ser Val Ala Ser Asp Asn Ala Ile ArgArg Ile Lys 2115 2120 2125 Pro Asp Gly Ser Ser Leu Met Asn Ile Val ThrHis Gly Ile Gly Glu 2130 2135 2140 Asn Gly Val Arg Gly Ile Ala Val AspTrp Val Ala Gly Asn Leu Tyr 2145 2150 2155 2160 Phe Thr Asn Ala Phe ValSer Glu Thr Leu Ile Glu Val Leu Arg Ile 2165 2170 2175 Asn Thr Thr TyrArg Arg Val Leu Leu Lys Val Thr Val Asp Met Pro 2180 2185 2190 Arg HisIle Val Val Asp Pro Lys Asn Arg Tyr Leu Phe Trp Ala Asp 2195 2200 2205Tyr Gly Gln Arg Pro Lys Ile Glu Arg Ser Phe Leu Asp Cys Thr Asn 22102215 2220 Arg Thr Val Leu Val Ser Glu Gly Ile Val Thr Pro Arg Gly LeuAla 2225 2230 2235 2240 Val Asp Arg Ser Asp Gly Tyr Val Tyr Trp Val AspAsp Ser Leu Asp 2245 2250 2255 Ile Ile Ala Arg Ile Arg Ile Asn Gly GluAsn Ser Glu Val Ile Arg 2260 2265 2270 Tyr Gly Ser Arg Tyr Pro Thr ProTyr Gly Ile Thr Val Phe Glu Asn 2275 2280 2285 Ser Ile Ile Trp Val AspArg Asn Leu Lys Lys Ile Phe Gln Ala Ser 2290 2295 2300 Lys Glu Pro GluAsn Thr Glu Pro Pro Thr Val Ile Arg Asp Asn Ile 2305 2310 2315 2320 AsnTrp Leu Arg Asp Val Thr Ile Phe Asp Lys Gln Val Gln Pro Arg 2325 23302335 Ser Pro Ala Glu Val Asn Asn Asn Pro Cys Leu Glu Asn Asn Gly Gly2340 2345 2350 Cys Ser His Leu Cys Phe Ala Leu Pro Gly Leu His Thr ProLys Cys 2355 2360 2365 Asp Cys Ala Phe Gly Thr Leu Gln Ser Asp Gly LysAsn Cys Ala Ile 2370 2375 2380 Ser Thr Glu Asn Phe Leu Ile Phe Ala LeuSer Asn Ser Leu Arg Ser 2385 2390 2395 2400 Leu His Leu Asp Pro Glu AsnHis Ser Pro Pro Phe Gln Thr Ile Asn 2405 2410 2415 Val Glu Arg Thr ValMet Ser Leu Asp Tyr Asp Ser Val Ser Asp Arg 2420 2425 2430 Ile Tyr PheThr Gln Asn Leu Ala Ser Gly Val Gly Gln Ile Ser Tyr 2435 2440 2445 AlaThr Leu Ser Ser Gly Ile His Thr Pro Thr Val Ile Ala Ser Gly 2450 24552460 Ile Gly Thr Ala Asp Gly Ile Ala Phe Asp Trp Ile Thr Arg Arg Ile2465 2470 2475 2480 Tyr Tyr Ser Asp Tyr Leu Asn Gln Met Ile Asn Ser MetAla Glu Asp 2485 2490 2495 Gly Ser Asn Arg Thr Val Ile Ala Arg Val ProLys Pro Arg Ala Ile 2500 2505 2510 Val Leu Asp Pro Cys Gln Gly Tyr LeuTyr Trp Ala Asp Trp Asp Thr 2515 2520 2525 His Ala Lys Ile Glu Arg AlaThr Leu Gly Gly Asn Phe Arg Val Pro 2530 2535 2540 Ile Val Asn Ser SerLeu Val Met Pro Ser Gly Leu Thr Leu Asp Tyr 2545 2550 2555 2560 Glu GluAsp Leu Leu Tyr Trp Val Asp Ala Ser Leu Gln Arg Ile Glu 2565 2570 2575Arg Ser Thr Leu Thr Gly Val Asp Arg Glu Val Ile Val Asn Ala Ala 25802585 2590 Val His Ala Phe Gly Leu Thr Leu Tyr Gly Gln Tyr Ile Tyr TrpThr 2595 2600 2605 Asp Leu Tyr Thr Gln Arg Ile Tyr Arg Ala Asn Lys TyrAsp Gly Ser 2610 2615 2620 Gly Gln Ile Ala Met Thr Thr Asn Leu Leu SerGln Pro Arg Gly Ile 2625 2630 2635 2640 Asn Thr Val Val Lys Asn Gln LysGln Gln Cys Asn Asn Pro Cys Glu 2645 2650 2655 Gln Phe Asn Gly Gly CysSer His Ile Cys Ala Pro Gly Pro Asn Gly 2660 2665 2670 Ala Glu Cys GlnCys Pro His Glu Gly Asn Trp Tyr Leu Ala Asn Asn 2675 2680 2685 Arg LysHis Cys Ile Val Asp Asn Gly Glu Arg Cys Gly Ala Ser Ser 2690 2695 2700Phe Thr Cys Ser Asn Gly Arg Cys Ile Ser Glu Glu Trp Lys Cys Asp 27052710 2715 2720 Asn Asp Asn Asp Cys Gly Asp Gly Ser Asp Glu Met Glu SerVal Cys 2725 2730 2735 Ala Leu His Thr Cys Ser Pro Thr Ala Phe Thr CysAla Asn Gly Arg 2740 2745 2750 Cys Val Gln Tyr Ser Tyr Arg Cys Asp TyrTyr Asn Asp Cys Gly Asp 2755 2760 2765 Gly Ser Asp Glu Ala Gly Cys LeuPhe Arg Asp Cys Asn Ala Thr Thr 2770 2775 2780 Glu Phe Met Cys Asn AsnArg Arg Cys Ile Pro Arg Glu Phe Ile Cys 2785 2790 2795 2800 Asn Gly ValAsp Asn Cys His Asp Asn Asn Thr Ser Asp Glu Lys Asn 2805 2810 2815 CysPro Asp Arg Thr Cys Gln Ser Gly Tyr Thr Lys Cys His Asn Ser 2820 28252830 Asn Ile Cys Ile Pro Arg Val Tyr Leu Cys Asp Gly Asp Asn Asp Cys2835 2840 2845 Gly Asp Asn Ser Asp Glu Asn Pro Thr Tyr Cys Thr Thr HisThr Cys 2850 2855 2860 Ser Ser Ser Glu Phe Gln Cys Ala Ser Gly Arg CysIle Pro Gln His 2865 2870 2875 2880 Trp Tyr Cys Asp Gln Glu Thr Asp CysPhe Asp Ala Ser Asp Glu Pro 2885 2890 2895 Ala Ser Cys Gly His Ser GluArg Thr Cys Leu Ala Asp Glu Phe Lys 2900 2905 2910 Cys Asp Gly Gly ArgCys Ile Pro Ser Glu Trp Ile Cys Asp Gly Asp 2915 2920 2925 Asn Asp CysGly Asp Met Ser Asp Glu Asp Lys Arg His Gln Cys Gln 2930 2935 2940 AsnGln Asn Cys Ser Asp Ser Glu Phe Leu Cys Val Asn Asp Arg Pro 2945 29502955 2960 Pro Asp Arg Arg Cys Ile Pro Gln Ser Trp Val Cys Asp Gly AspVal 2965 2970 2975 Asp Cys Thr Asp Gly Tyr Asp Glu Asn Gln Asn Cys ThrArg Arg Thr 2980 2985 2990 Cys Ser Glu Asn Glu Phe Thr Cys Gly Tyr GlyLeu Cys Ile Pro Lys 2995 3000 3005 Ile Phe Arg Cys Asp Arg His Asn AspCys Gly Asp Tyr Ser Asp Glu 3010 3015 3020 Arg Gly Cys Leu Tyr Gln ThrCys Gln Gln Asn Gln Phe Thr Cys Gln 3025 3030 3035 3040 Asn Gly Arg CysIle Ser Lys Thr Phe Val Cys Asp Glu Asp Asn Asp 3045 3050 3055 Cys GlyAsp Gly Ser Asp Glu Leu Met His Leu Cys His Thr Pro Glu 3060 3065 3070Pro Thr Cys Pro Pro His Glu Phe Lys Cys Asp Asn Gly Arg Cys Ile 30753080 3085 Glu Met Met Lys Leu Cys Asn His Leu Asp Asp Cys Leu Asp AsnSer 3090 3095 3100 Asp Glu Lys Gly Cys Gly Ile Asn Glu Cys His Asp ProSer Ile Ser 3105 3110 3115 3120 Gly Cys Asp His Asn Cys Thr Asp Thr LeuThr Ser Phe Tyr Cys Ser 3125 3130 3135 Cys Arg Pro Gly Tyr Lys Leu MetSer Asp Lys Arg Thr Cys Val Asp 3140 3145 3150 Ile Asp Glu Cys Thr GluMet Pro Phe Val Cys Ser Gln Lys Cys Glu 3155 3160 3165 Asn Val Ile GlySer Tyr Ile Cys Lys Cys Ala Pro Gly Tyr Leu Arg 3170 3175 3180 Glu ProAsp Gly Lys Thr Cys Arg Gln Asn Ser Asn Ile Glu Pro Tyr 3185 3190 31953200 Leu Ile Phe Ser Asn Arg Tyr Tyr Leu Arg Asn Leu Thr Ile Asp Gly3205 3210 3215 Tyr Phe Tyr Ser Leu Ile Leu Glu Gly Leu Asp Asn Val ValAla Leu 3220 3225 3230 Asp Phe Asp Arg Val Glu Lys Arg Leu Tyr Trp IleAsp Thr Gln Arg 3235 3240 3245 Gln Val Ile Glu Arg Met Phe Leu Asn LysThr Asn Lys Glu Thr Ile 3250 3255 3260 Ile Asn His Arg Leu Pro Ala AlaGlu Ser Leu Ala Val Asp Trp Val 3265 3270 3275 3280 Ser Arg Lys Leu TyrTrp Leu Asp Ala Arg Leu Asp Gly Leu Phe Val 3285 3290 3295 Ser Asp LeuAsn Gly Gly His Arg Arg Met Leu Ala Gln His Cys Val 3300 3305 3310 AspAla Asn Asn Thr Phe Cys Phe Asp Asn Pro Arg Gly Leu Ala Leu 3315 33203325 His Pro Gln Tyr Gly Tyr Leu Tyr Trp Ala Asp Trp Gly His Arg Ala3330 3335 3340 Tyr Ile Gly Arg Val Gly Met Asp Gly Thr Asn Lys Ser ValIle Ile 3345 3350 3355 3360 Ser Thr Lys Leu Glu Trp Pro Asn Gly Ile ThrIle Asp Tyr Thr Asn 3365 3370 3375 Asp Leu Leu Tyr Trp Ala Asp Ala HisLeu Gly Tyr Ile Glu Tyr Ser 3380 3385 3390 Asp Leu Glu Gly His His ArgHis Thr Val Tyr Asp Gly Ala Leu Pro 3395 3400 3405 His Pro Phe Ala IleThr Ile Phe Glu Asp Thr Ile Tyr Trp Thr Asp 3410 3415 3420 Trp Asn ThrArg Thr Val Glu Lys Gly Asn Lys Tyr Asp Gly Ser Asn 3425 3430 3435 3440Arg Gln Thr Leu Val Asn Thr Thr His Arg Pro Phe Asp Ile His Val 34453450 3455 Tyr His Pro Tyr Arg Gln Pro Ile Val Ser Asn Pro Cys Gly ThrAsn 3460 3465 3470 Asn Gly Gly Cys Ser His Leu Cys Leu Ile Lys Pro GlyGly Lys Gly 3475 3480 3485 Phe Thr Cys Glu Cys Pro Asp Asp Phe Arg ThrLeu Gln Leu Ser Gly 3490 3495 3500 Ser Thr Tyr Cys Met Pro Met Cys SerSer Thr Gln Phe Leu Cys Ala 3505 3510 3515 3520 Asn Asn Glu Lys Cys IlePro Ile Trp Trp Lys Cys Asp Gly Gln Lys 3525 3530 3535 Asp Cys Ser AspGly Ser Asp Glu Leu Ala Leu Cys Pro Gln Arg Phe 3540 3545 3550 Cys ArgLeu Gly Gln Phe Gln Cys Ser Asp Gly Asn Cys Thr Ser Pro 3555 3560 3565Gln Thr Leu Cys Asn Ala His Gln Asn Cys Pro Asp Gly Ser Asp Glu 35703575 3580 Asp Arg Leu Leu Cys Glu Asn His His Cys Asp Ser Asn Glu TrpGln 3585 3590 3595 3600 Cys Ala Asn Lys Arg Cys Ile Pro Glu Ser Trp GlnCys Asp Thr Phe 3605 3610 3615 Asn Asp Cys Glu Asp Asn Ser Asp Glu AspSer Ser His Cys Ala Ser 3620 3625 3630 Arg Thr Cys Arg Pro Gly Gln PheArg Cys Ala Asn Gly Arg Cys Ile 3635 3640 3645 Pro Gln Ala Trp Lys CysAsp Val Asp Asn Asp Cys Gly Asp His Ser 3650 3655 3660 Asp Glu Pro IleGlu Glu Cys Met Ser Ser Ala His Leu Cys Asp Asn 3665 3670 3675 3680 PheThr Glu Phe Ser Cys Lys Thr Asn Tyr Arg Cys Ile Pro Lys Trp 3685 36903695 Ala Val Cys Asn Gly Val Asp Asp Cys Arg Asp Asn Ser Asp Glu Gln3700 3705 3710 Gly Cys Glu Glu Arg Thr Cys His Pro Val Gly Asp Phe ArgCys Lys 3715 3720 3725 Asn His His Cys Ile Pro Leu Arg Trp Gln Cys AspGly Gln Asn Asp 3730 3735 3740 Cys Gly Asp Asn Ser Asp Glu Glu Asn CysAla Pro Arg Glu Cys Thr 3745 3750 3755 3760 Glu Ser Glu Phe Arg Cys ValAsn Gln Gln Cys Ile Pro Ser Arg Trp 3765 3770 3775 Ile Cys Asp His TyrAsn Asp Cys Gly Asp Asn Ser Asp Glu Arg Asp 3780 3785 3790 Cys Glu MetArg Thr Cys His Pro Glu Tyr Phe Gln Cys Thr Ser Gly 3795 3800 3805 HisCys Val His Ser Glu Leu Lys Cys Asp Gly Ser Ala Asp Cys Leu 3810 38153820 Asp Ala Ser Asp Glu Ala Asp Cys Pro Thr Arg Phe Pro Asp Gly Ala3825 3830 3835 3840 Tyr Cys Gln Ala Thr Met Phe Glu Cys Lys Asn His ValCys Ile Pro 3845 3850 3855 Pro Tyr Trp Lys Cys Asp Gly Asp Asp Asp CysGly Asp Gly Ser Asp 3860 3865 3870 Glu Glu Leu His Leu Cys Leu Asp ValPro Cys Asn Ser Pro Asn Arg 3875 3880 3885 Phe Arg Cys Asp Asn Asn ArgCys Ile Tyr Ser His Glu Val Cys Asn 3890 3895 3900 Gly Val Asp Asp CysGly Asp Gly Thr Asp Glu Thr Glu Glu His Cys 3905 3910 3915 3920 Arg LysPro Thr Pro Lys Pro Cys Thr Glu Tyr Glu Tyr Lys Cys Gly 3925 3930 3935Asn Gly His Cys Ile Pro His Asp Asn Val Cys Asp Asp Ala Asp Asp 39403945 3950 Cys Gly Asp Trp Ser Asp Glu Leu Gly Cys Asn Lys Gly Lys GluArg 3955 3960 3965 Thr Cys Ala Glu Asn Ile Cys Glu Gln Asn Cys Thr GlnLeu Asn Glu 3970 3975 3980 Gly Gly Phe Ile Cys Ser Cys Thr Ala Gly PheGlu Thr Asn Val Phe 3985 3990 3995 4000 Asp Arg Thr Ser Cys Leu Asp IleAsn Glu Cys Glu Gln Phe Gly Thr 4005 4010 4015 Cys Pro Gln His Cys ArgAsn Thr Lys Gly Ser Tyr Glu Cys Val Cys 4020 4025 4030 Ala Asp Gly PheThr Ser Met Ser Asp Arg Pro Gly Lys Arg Cys Ala 4035 4040 4045 Ala GluGly Ser Ser Pro Leu Leu Leu Leu Pro Asp Asn Val Arg Ile 4050 4055 4060Arg Lys Tyr Asn Leu Ser Ser Glu Arg Phe Ser Glu Tyr Leu Gln Asp 40654070 4075 4080 Glu Glu Tyr Ile Gln Ala Val Asp Tyr Asp Trp Asp Pro GluAsp Ile 4085 4090 4095 Gly Leu Ser Val Val Tyr Tyr Thr Val Arg Gly GluGly Ser Arg Phe 4100 4105 4110 Gly Ala Ile Lys Arg Ala Tyr Ile Pro AsnPhe Glu Ser Gly Arg Asn 4115 4120 4125 Asn Leu Val Gln Glu Val Asp LeuLys Leu Lys Tyr Val Met Gln Pro 4130 4135 4140 Asp Gly Ile Ala Val AspTrp Val Gly Arg His Ile Tyr Trp Ser Asp 4145 4150 4155 4160 Val Lys AsnLys Arg Ile Glu Val Ala Lys Leu Asp Gly Arg Tyr Arg 4165 4170 4175 LysTrp Leu Ile Ser Thr Asp Leu Asp Gln Pro Ala Ala Ile Ala Val 4180 41854190 Asn Pro Lys Leu Gly Leu Met Phe Trp Thr Asp Trp Gly Lys Glu Pro4195 4200 4205 Lys Leu Glu Ser Ala Trp Met Asn Gly Glu Asp Arg Asn IleLeu Val 4210 4215 4220 Phe Glu Asp Leu Gly Trp Pro Thr Gly Leu Ser IleAsp Tyr Leu Asn 4225 4230 4235 4240 Asn Asp Arg Ile Tyr Trp Ser Asp PheLys Glu Asp Val Ile Glu Thr 4245 4250 4255 Ile Lys Tyr Asp Gly Thr AspArg Arg Val Ile Ala Lys Glu Ala Met 4260 4265 4270 Asn Pro Tyr Ser LeuAsp Ile Phe Glu Asp Gln Leu Tyr Trp Ile Ser 4275 4280 4285 Lys Glu LysGly Glu Val Trp Lys Gln Asn Lys Phe Gly Gln Gly Lys 4290 4295 4300 LysGlu Lys Thr Leu Val Val Asn Pro Trp Leu Thr Gln Val Arg Ile 4305 43104315 4320 Phe His Gln Leu Arg Tyr Asn Lys Ser Val Pro Asn Leu Cys LysGln 4325 4330 4335 Ile Cys Ser His Leu Cys Leu Leu Arg Pro Gly Gly TyrSer Cys Ala 4340 4345 4350 Cys Pro Gln Gly Ser Ser Phe Ile Glu Gly SerThr Thr Glu Cys Asp 4355 4360 4365 Ala Ala Ile Glu Leu Pro Ile Asn LeuPro Pro Pro Cys Arg Cys Met 4370 4375 4380 His Gly Gly Asn Cys Tyr PheAsp Glu Thr Asp Leu Pro Lys Cys Lys 4385 4390 4395 4400 Cys Pro Ser GlyTyr Thr Gly Lys Tyr Cys Glu Met Ala Phe Ser Lys 4405 4410 4415 Gly IleSer Pro Gly Thr Thr Ala Val Ala Val Leu Leu Thr Ile Leu 4420 4425 4430Leu Ile Val Val Ile Gly Ala Leu Ala Ile Ala Gly Phe Phe His Tyr 44354440 4445 Arg Arg Thr Gly Ser Leu Leu Pro Ala Leu Pro Lys Leu Pro SerLeu 4450 4455 4460 Ser Ser Leu Val Lys Pro Ser Glu Asn Gly Asn Gly ValThr Phe Arg 4465 4470 4475 4480 Ser Gly Ala Asp Leu Asn Met Asp Ile GlyVal Ser Gly Phe Gly Pro 4485 4490 4495 Glu Thr Ala Ile Asp Arg Ser MetAla Met Ser Glu Asp Phe Val Met 4500 4505 4510 Glu Met Gly Lys Gln ProIle Ile Phe Glu Asn Pro Met Tyr Ser Ala 4515 4520 4525 Arg Asp Ser AlaVal Lys Val Val Gln Pro Ile Gln Val Thr Val Ser 4530 4535 4540 Glu AsnVal Asp Asn Lys Asn Tyr Gly Ser Pro Ile Asn Pro Ser Glu 4545 4550 45554560 Ile Val Pro Glu Thr Asn Pro Thr Ser Pro Ala Ala Asp Gly Thr Gln4565 4570 4575 Val Thr Lys Trp Asn Leu Phe Lys Arg Lys Ser Lys Gln ThrThr Asn 4580 4585 4590 Phe Glu Asn Pro Ile Tyr Ala Gln Met Glu Asn GluGln Lys Glu Ser 4595 4600 4605 Val Ala Ala Thr Pro Pro Pro Ser Pro SerLeu Pro Ala Lys Pro Lys 4610 4615 4620 Pro Pro Ser Arg Arg Asp Pro ThrPro Thr Tyr Ser Ala Thr Glu Asp 4625 4630 4635 4640 Thr Phe Lys Asp ThrAla Asn Leu Val Lys Glu Asp Ser Glu Val 4645 4650 4655 19 base pairsnucleic acid single linear other nucleic acid NO NO unknown 91GCAGACCTAA AGGAGCGTT 19 20 base pairs nucleic acid single linear othernucleic acid NO NO unknown 92 CCCGACCATT GGAGAAGATA 20 19 base pairsnucleic acid single linear other nucleic acid NO NO unknown 93GCCAGTACCA GTGCCATGA 19 21 base pairs nucleic acid single linear othernucleic acid NO NO unknown 94 CCTCATGACA CTGATACTCT T 21 18 base pairsnucleic acid single linear other nucleic acid NO NO unknown 95GGCTGTGAGC AGGTCTGT 18 23 base pairs nucleic acid single linear othernucleic acid NO NO unknown 96 CGACCACTAA TTGAATCAAA ATC 23 19 base pairsnucleic acid single linear other nucleic acid NO NO unknown 97CGGTGCTCGT GTGATACAG 19 18 base pairs nucleic acid single linear othernucleic acid NO NO unknown 98 ATCCACATCC ACATGCAG 18 22 base pairsnucleic acid single linear other nucleic acid NO NO unknown 99CCTCAAATGG CTGTAGCAAC AA 22 18 base pairs nucleic acid single linearother nucleic acid NO NO unknown 100 CTGCTGCTGC ACGTGTGA 18 22 basepairs nucleic acid single linear other nucleic acid NO NO unknown 101CCAGTCTGGA TACACAAAAT GT 22 15 base pairs nucleic acid single linearother nucleic acid NO NO unknown 102 GGCGCACTGC CATTC 15 21 base pairsnucleic acid single linear other nucleic acid NO NO unknown 103CTCAGATGGC TCTGATGAAC T 21 21 base pairs nucleic acid single linearother nucleic acid NO NO unknown 104 GCGTTTTCTC TTTCTTTCCT T 21 22 basepairs nucleic acid single linear other nucleic acid NO NO unknown 105GAGAGTCATT GCAAAGGAAG CA 22 23 base pairs nucleic acid single linearother nucleic acid NO NO unknown 106 AATATATGTG CAAAAGTGTG TTT 23

What is claimed is:
 1. A method of identifying a compound that eitherblocks or enhances the activity of human gp330, comprising: (A)expressing in a heterologous host cell a nucleic acid encoding a proteincomprising an amino acid sequence selected from the group consisting ofSEQ ID No. 4, SEQ ID No. 12, SEQ ID No.84, SEQ ID No.86, SEQ ID No.88,and SEQ ID No. 90; (B) contacting the compound with said host cell; and(C) determining the ability of said compound to block or enhance theactivity of said gp330.
 2. The method of claim 1, wherein said activityis uptake and transport of amyloid protein.